J. Cell. Physiol. [JOURNAL]
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200 papers
Scaffold Protein PDLIM5 Regulates TRPC1 Calcium Channel Mediated Store-Operated Calcium Entry in Mouse Myoblasts.
Dong M, Niimi T, Maturana AD
J Cell Physiol · 2026 May · PMID 42083336 · Publisher ↗
Intracellular calcium (Ca) signaling controls myoblast proliferation, fusion, and myofiber formation. In myoblasts, Transient Receptor Potential Canonical (TRPC) channels, with TRPC1 as a predominant isoform, mediate sto...
Intracellular calcium (Ca) signaling controls myoblast proliferation, fusion, and myofiber formation. In myoblasts, Transient Receptor Potential Canonical (TRPC) channels, with TRPC1 as a predominant isoform, mediate store-operated Ca²⁺ entry (SOCE) and are essential for myogenesis. PDLIM5 (ENH1), a PDZ-LIM scaffold protein, organizes signaling events, including ion channel regulation and transcriptional control in muscles. This study aims to test the hypothesis that PDLIM5 regulates TRPC1-mediated Ca entry in myoblasts. Thapsigargin-induced SOCE was suppressed by the SOCE inhibitors Gd and 2-APB, as well as by TRPC1 siRNA, supporting the involvement of TRPC1 in SOCE in C2C12 myoblasts. Additionally, SOCE inhibition decreased the number of nuclei per myotube and reduced the size of myotubes. ENH1 siRNA knockdown significantly downregulated TRPC1 and STIM1 mRNA expression, increased basal cytosolic Ca level, and impaired SOCE response and myotube maturation. Overexpression of ENH4, a skeletal muscle-specific short splice variant of ENH1, similarly repressed TRPC1-mediated SOCE and myotube formation. Conversely, ENH1 overexpression enhanced SOCE without altering the mRNA levels of TRPC1, Orai1, or STIM1. Immunoprecipitation showed a physical interaction between ENH1/ENH4 and TRPC1. In differentiated myotubes, TRPC1 also contributed to thapsigargin-induced SOCE, as evidenced by the reduced Ca entry following TRPC1 knockdown. ENH1 knockdown and ENH4 overexpression significantly attenuated SOCE in myotubes; notably, ENH1 knockdown also increased basal cytosolic Ca level. In contrast to myoblasts, ENH1 overexpression did not enhance SOCE in myotubes, concomitant with the absence of a detectable interaction between ENH1 and TRPC1, whereas ENH4 retained its association with TRPC1. These findings suggest that ENH1 and ENH4 differentially modulate TRPC1-dependent Ca entry in C2C12 cells, thereby regulating myogenic differentiation and contributing to skeletal muscle formation and development.
Hematopoietic Stem Cell Tropism Mediated Targeting of Breast Cancer Stem Cells via Alteration of Tumor Immune-Microenvironment.
Mallick S, Biswas S, Shenoy P S … +1 more , Bose B
J Cell Physiol · 2026 May · PMID 42083305 · Publisher ↗
The ontogenic development of hematopoietic stem cells (HSCs) occurs across diverse niches, with HSCs migrating from the aorta-gonad-mesonephros (AGM) to the fetal liver and finally residing in the bone marrow after birth...
The ontogenic development of hematopoietic stem cells (HSCs) occurs across diverse niches, with HSCs migrating from the aorta-gonad-mesonephros (AGM) to the fetal liver and finally residing in the bone marrow after birth, where adult HSCs replenish the hematopoietic system. The HSC niche critically regulates tropism and proliferation via factors secreted by the microenvironment interaction. Here, we hypothesized that HSCs display tropism toward the aggressive cancer stem cell (CSC) niches of triple-negative breast cancer (TNBC) and MCF-7 cells breast cancer, which exhibit high relapse rates and are potential targets for cell therapy. Our results demonstrate HSC-specific tropism toward breast CSCs, leading to interactions that trigger HSC differentiation into CD4 and CD8 subpopulations within the cancer microenvironment. Proteomics of migrated HSCs toward TNBC-CSCs/MCF-7 cells revealed significant upregulation of IL-7, Notch, and other proteins involved in T cell activation and migration pathways. Metabolomics of HSC-conditioned medium (HSC-CM)-treated CSCs/MCF-7 cells further demonstrated that HSC-CM arrests TNBC-CSC growth and cell cycle progression by altering the mitochondrial bioenergetics. This study highlights the potential of leveraging both HSCs and HSC-derived factors for personalized therapies targeting CSCs in TNBC.
Molecular Mechanisms of Programmed Cell Death Pathways in Chronic Obstructive Pulmonary Disease.
Zhuang Y, Yao L, Qi W
J Cell Physiol · 2026 May · PMID 42077197 · Publisher ↗
Chronic obstructive pulmonary disease (COPD) represents a prevalent respiratory ailment, which is distinguished by enduring airflow obstruction and a tendency to progress over time. Over 400 million people globally are c...
Chronic obstructive pulmonary disease (COPD) represents a prevalent respiratory ailment, which is distinguished by enduring airflow obstruction and a tendency to progress over time. Over 400 million people globally are currently impacted. Alveolar epithelial cells, airway epithelial cells, and important inflammatory cell populations are all actively involved in the pathological development of COPD. These cells' interactions have wide-ranging physiological effects on the body, such as aggravating lung damage and inducing inflammation, which are the pathogenic causes of COPD. In the present review, numerous programmed cell death (PCD) modes are addressed with a focus on molecular mechanisms and crosstalk of seven PCD processes-apoptosis, necroptosis, ferroptosis, autophagy, pyroptosis, cuproptosis, and disulfidptosis-in COPD pathogenesis and initiation. It also refers to clinical treatment strategies for the acute and stable phases of COPD based on PCD regulation. From the cellular perspective, we may have a more exact understanding of disease phenotypes; demystification of cell-type-specific mechanisms is aimed at providing theoretical guidance for further probing of COPD's molecular pathology and development of novel therapeutic strategies against PCD.
Maternal Obesity Programs Adipogenic Commitment in Neonatal Mesenchymal Stem Cells: A Link to Redox-Dependent FOXO1 Signaling.
Bellalta S, Pinheiro-Machado E, Borghuis T … +4 more , Prins J, Plösch T, Casanello P, Faas M
J Cell Physiol · 2026 Apr · PMID 42047265 · Full text
Maternal obesity increases the risk of obesity and metabolic disease in the offspring, yet the cellular mechanisms that program adipose tissue development remain poorly understood. Mesenchymal stem cells (MSCs), the prec...
Maternal obesity increases the risk of obesity and metabolic disease in the offspring, yet the cellular mechanisms that program adipose tissue development remain poorly understood. Mesenchymal stem cells (MSCs), the precursors of adipocytes, may represent an early target of metabolic programming during fetal development. In this study, we investigated whether maternal obesity alters stemness, redox homeostasis and adipogenic signaling through FOXO1 in neonatal MSCs. MSCs were isolated from Wharton's jelly of umbilical cords from neonates born to mothers with normal weight (NW-MSCs, n = 15) or obesity (OB-MSCs, n = 15). OB-MSCs exhibited reduced stemness characteristics, including lower OCT3/4 expression and decreased clonogenic capacity. These cells also displayed increased mitochondrial superoxide levels and reduced SOD2 expression, indicating mitochondrial oxidative stress. In addition, OB-MSCs showed increased GSH levels and decreased antioxidant enzyme response, compared to NW-MSCs. Further, OB-MSCs exhibited higher FOXO1 expression levels, reduced acetyl-FOXO1 levels, and altered subcellular localization during early adipogenesis, consistent with reduced repression of the adipogenic regulator PPARγ. Finally, OB-MSC-derived adipocytes exhibited increased PPARγ expression at later stages of differentiation. These findings suggest that maternal obesity disrupts redox balance and FOXO1 dynamics in neonatal MSCs, thereby shifting early adipogenic signaling toward enhanced adipocyte commitment. This early programming mechanism may expand the adipocyte precursor pool, potentially predisposing the progeny to higher adiposity and metabolic disorders later in life.
Novel Regulatory Cell Death in Intervertebral Disc Degeneration.
Zhang X, Liu Z, Chen Y … +6 more , Bai F, Zhang Y, Li M, Yan S, Luo Z, Ding M
J Cell Physiol · 2026 Apr · PMID 42047245 · Publisher ↗
Intervertebral disc degeneration (IDD) is a major cause of chronic low back pain. Its pathogenesis is highly complex and encompasses multiple pathological processes, including cellular dysfunction, extracellular matrix (...
Intervertebral disc degeneration (IDD) is a major cause of chronic low back pain. Its pathogenesis is highly complex and encompasses multiple pathological processes, including cellular dysfunction, extracellular matrix (ECM) degradation, inflammatory responses, oxidative stress, and aberrant mechanical loading. Traditionally, programmed cell death (PCD), particularly apoptosis and autophagy, has been regarded as a key contributor to IDD. However, with ongoing advances in this field, an expanding number of emerging forms of regulated cell death (RCD) have been identified and demonstrated to play critical roles in the initiation and progression of IDD. These advances have also provided new insights into the key molecular events underlying disc degeneration and have facilitated the identification of potential disease-modifying therapeutic targets. This review systematically summarizes five emerging RCD modalities, namely ferroptosis, cuproptosis, necroptosis, PANoptosis, and disulfidptosis, with particular emphasis on their mechanistic roles, key regulatory factors, signaling pathways, and patterns of interaction in IDD. Current evidence indicates that these RCD modalities not only independently contribute to cell death but may also converge through shared pathological nodes, including oxidative stress, mitochondrial dysfunction, and inflammatory signaling, thereby producing synergistic amplification effects that further aggravate cell loss and matrix destruction. Regarding therapeutic strategies, a range of RCD-targeted pharmacological approaches has been reported to exhibit potential therapeutic value, including iron chelators, modulators of copper metabolism, inhibitors of the RIPK signaling pathway, antioxidants, and agents targeting PANoptosis-related signaling. These findings provide novel perspectives for the precision treatment of IDD. Nevertheless, most available studies remain limited to cellular and animal models, and the spatiotemporal expression patterns of the relevant signaling networks, their mechanisms of interaction, and their dynamic changes across different stages of degeneration remain to be further elucidated. Taken together, the identification of emerging RCD mechanisms has provided a more comprehensive framework for understanding the complex pathological processes of IDD. Furthermore, it has established a theoretical basis for the development of multi-target combinatorial intervention strategies and disease-modifying therapeutic paradigms, and may ultimately facilitate a shift in IDD management from symptomatic relief alone toward etiology-oriented and precision-based interventions.
Reversible Nucleolar Stress and Cell Growth Arrest Triggered by Acidic pH.
de Mesquita CB, Kaida A, Nojima H … +1 more , Miura M
J Cell Physiol · 2026 Apr · PMID 41995092 · Full text
The tumor microenvironment is often characterized by hypoxia and extracellular acidosis, which modulate various tumor cell phenotypes. Ribosome biogenesis is a highly energy-demanding process that is essential for protei...
The tumor microenvironment is often characterized by hypoxia and extracellular acidosis, which modulate various tumor cell phenotypes. Ribosome biogenesis is a highly energy-demanding process that is essential for protein synthesis and cell proliferation and is sensitive to cellular stress, resulting in a nucleolar stress response. However, whether extracellular acidosis impairs ribosome biogenesis and induces nucleolar stress remains unclear. In this study, we demonstrated that an acidic pH downregulates ribosome biogenesis in cancer cells. RNA sequencing revealed the downregulation of genes related to ribosome biogenesis and cell cycle progression under acidic conditions. Consistently, acidic pH reduced the pre-rRNA levels and induced nucleolar stress, as evidenced by NPM1 translocation from the nucleolus to the nucleoplasm, which led to G1 phase arrest and growth inhibition. Importantly, these effects were reversed upon restoration of neutral pH, with recovery of pre-rRNA expression, NPM1 localization, and cell proliferation. Further, an acidic pH shifted the intracellular redox balance toward an oxidized state. Treatment with the reductant dithiothreitol partially reversed NPM1 translocation, suggesting that oxidative stress contributes, at least partially, to the nucleolar stress response. Overall, our findings reveal a previously unrecognized link between extracellular acidosis and impaired ribosome biogenesis, leading to nucleolar stress and reversible growth arrest. This acidosis-driven stress response represents a therapeutic vulnerability in solid tumors, offering a novel strategy to overcome treatment resistance associated with the acidic tumor microenvironment.
Correction to "FGF21 Impedes Peripheral Myelin Development by Stimulating p38 MAPK/c-Jun Axis".
J Cell Physiol · 2026 Apr · PMID 41995084 · Publisher ↗
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Tooth Decay Promotes Senescence in Dental Pulp Stem Cells, Modifying Their Biological and Proteomic Profiles.
Durukan SM, Acar MB, Tez BÇ … +11 more , Şimşek A, Al-Sammarrie SHA, Günaydın Z, Güzel M, Süer BB, Güner ŞA, Güner H, Alessio N, Başaran KE, Gönen ZB, Özcan S
J Cell Physiol · 2026 Apr · PMID 41987558 · Full text
Dental caries is a prevalent oral health problem that significantly reduces an individual's quality of life; although, it can be effectively managed through restorative treatments. Even in cases where the caries does not...
Dental caries is a prevalent oral health problem that significantly reduces an individual's quality of life; although, it can be effectively managed through restorative treatments. Even in cases where the caries does not reach the pulp, released microbial products from the lesion can still penetrate the pulp chamber, potentially inducing stress on pulp cells. In this study, we conducted a comparative analysis of the biological and proteomic profiles of dental pulp stem cells (DPSCs) isolated from clinically asymptomatic teeth with dentinal caries that had not reached the pulp and isolated from healthy teeth. Following biological evaluations, we examined proteomes of these DPSCs by conducting a shotgun proteomics approach. Our findings show that DPSCs from decayed teeth exhibit a significantly higher proportion of senescent cells. Proteomic profiling revealed upregulation of inflammatory signaling, extracellular matrix remodeling, and senescence-associated secretory phenotype (SASP) related proteins. Additionally, we observed an upregulation in the expression of proteins associated with extracellular matrix (ECM) remodeling and components of the SASP, which are hallmarks of the senescence process. The study reveals that DPSCs can be affected by stress from carious lesions, even when the pulp appears clinically intact. Senescence and inflammatory response in these affected cells may have deleterious effects on other tissues within the organism. Consequently, restorative treatments should consider targeting not only the decayed tissue but also the senescent cells within the pulp that may have been affected by the stress induced by caries.
Rh3R Attenuates RANKL-Induced Osteoclast Differentiation and F-Actin Ring Formation via the Suppression of c-Fos/NFATc1 Signaling in Primary Murine Cells.
Yun HM, Kim SH, Lee J … +1 more , Park KR
J Cell Physiol · 2026 Apr · PMID 41987536 · Publisher ↗
The homeostatic balance of bone remodeling is governed by the precise coordination between bone-forming osteoblasts and bone-resorbing osteoclasts. In this study, we investigated the anti-resorptive properties of rhamnoc...
The homeostatic balance of bone remodeling is governed by the precise coordination between bone-forming osteoblasts and bone-resorbing osteoclasts. In this study, we investigated the anti-resorptive properties of rhamnocitrin-3-rhamnoside (Rh3R), a flavonoid isolated from Loranthus tanakae, using primary bone marrow-derived macrophages (BMMs) and calvaria-derived osteogenic progenitor cells (COCs) to ensure biological relevance. Our findings demonstrate that Rh3R potently inhibits the RANKL-induced differentiation of BMMs into TRAP-positive multinucleated osteoclasts in a dose-dependent manner, without inducing cytotoxicity. Mechanistically, Rh3R effectively attenuates RANKL-induced downstream signaling cascades, as evidenced by the attenuated phosphorylation of MAPKs (ERK1/2, JNK, p38), AKT, and IκB. This signaling blockade subsequently suppresses the induction of the master transcription factors, c-Fos and NFATc1. Furthermore, Rh3R impairs the functional resorptive capacity of mature osteoclasts by destabilizing F-actin-rich ring structures accompanied by decreased integrin β3 expression, thereby preventing the formation of a functional sealing zone. The inhibitory effect of Rh3R on bone-degrading activity was further confirmed by a significant reduction in the total area of resorption pits on bone slices. Notably, Rh3R exhibits a lineage-specific inhibitory effect, showing no adverse influence on osteoblastogenesis or the mineralizing capacity of primary osteogenic cells. Furthermore, the effect of Rh3R was consistently maintained in a co-culture system of primary osteoblasts and BMMs. Collectively, these in vitro findings identify Rh3R as a bioactive modulator of osteoclast differentiation and function via suppression of RANKL-induced downstream signaling, warranting future in vivo and pharmacological studies to evaluate efficacy, exposure, and safety.
Clock Modulation by Naringenin Suppresses Lipogenesis and Promotes Adipose Tissue Browning.
Xiong X, Pangemanan J, Kiperman T … +4 more , Sun Z, Paul A, Yechoor V, Ma K
J Cell Physiol · 2026 Apr · PMID 41987529 · Full text
The circadian clock orchestrates adipocyte development and lipid remodeling, with its disruption leading to the development of obesity and insulin resistance. Here we demonstrate that the flavonoid compound naringenin di...
The circadian clock orchestrates adipocyte development and lipid remodeling, with its disruption leading to the development of obesity and insulin resistance. Here we demonstrate that the flavonoid compound naringenin displays clock modulatory activity that suppresses adipocyte lipid storage while promoting browning. In adipogenic progenitors, naringenin activates RORα with induction of clock gene expression to promote circadian clock oscillation with protective effect against cytokine-induced dampening. The clock-enhancing properties of naringenin suppressed lipogenesis in mature adipocytes together with induction of browning characteristics. The inhibitory effect of naringenin on lipogenesis was dependent on clock modulation as it was abolished in RORα-deficient adipocytes. We further show that naringenin administration in vivo up-regulated RORα expression with clock gene induction together with browning of subcutaneous beige fat depot, resulting reduced fat mass and body weight. Naringenin treatment in vivo also lowered plasma glucose and free fatty acid levels, with markedly enhanced insulin signaling in adipose depots and skeletal muscle. Collectively, our findings uncover a new clock-activating mechanism of action in mediating the metabolic benefits of naringenin, suggesting its potential as a natural supplement for anti-obesity and metabolic disease interventions.
RETRACTION: MicroRNA-6869-5p Acts as a Tumor Suppressor via Targeting TLR4/NF-κB Signaling Pathway in Colorectal Cancer.
J Cell Physiol · 2026 Apr · PMID 41982107 · Publisher ↗
RETRACTION: "MicroRNA-6869-5p Acts as a Tumor Suppressor via Targeting TLR4/NF-κB Signaling Pathway in Colorectal Cancer," by S. Yan, G. Liu, C. Jin, Z. Wang, Q. Duan, J. Xu, and D. Xu, Journal of Cellular Physiology 233...
RETRACTION: "MicroRNA-6869-5p Acts as a Tumor Suppressor via Targeting TLR4/NF-κB Signaling Pathway in Colorectal Cancer," by S. Yan, G. Liu, C. Jin, Z. Wang, Q. Duan, J. Xu, and D. Xu, Journal of Cellular Physiology 233, no. 9 (2018): 6660-6668, https://doi.org/10.1002/jcp.26316. The above article, published online on December 5, 2017 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Robert Heath; and Wiley Periodicals LLC. The retraction has been agreed due to concerns raised by third parties. Specifically, Figure 5A presents panels previously published by the author group in a different scientific context. Furthermore, scientific inconsistencies have been identified related to the patient data. The authors did not respond to our request for comments. Accordingly, the article has been retracted as the editors have lost confidence in the accuracy and integrity of the whole body of data and consider the conclusions of the article invalid. The authors were informed of the retraction decision but were unavailable for final confirmation.
Correction to "PIEZO1 Channels Modulate the Small Extracellular Vesicle Release in C2C12 Cells".
J Cell Physiol · 2026 Apr · PMID 41982091 · Publisher ↗
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RETRACTION: Exosome-Encapsulated miR-6089 Regulates Inflammatory Response via Targeting TLR4.
J Cell Physiol · 2026 Apr · PMID 41982088 · Publisher ↗
RETRACTION: "Exosome-Encapsulated miR-6089 Regulates Inflammatory Response via Targeting TLR4," by D. Xu, M. Song, C. Chai, H. et al., Journal of Cellular Physiology 234, no. 2 (2019): 1502-1511, https://doi.org/10.1002/...
RETRACTION: "Exosome-Encapsulated miR-6089 Regulates Inflammatory Response via Targeting TLR4," by D. Xu, M. Song, C. Chai, H. et al., Journal of Cellular Physiology 234, no. 2 (2019): 1502-1511, https://doi.org/10.1002/jcp.27014. The above article, published online on 21 August 2018 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Robert Heath, and Wiley Periodicals LLC. The retraction has been agreed due to concerns raised by third parties. Specifically, image elements in Figure 4F were found to have been previously published by the author group in a different scientific context. Furthermore, scientific inconsistencies were identified that undermine the study's rationale, and the article lacks essential information required to interpret and reproduce the findings. The authors did not respond to our request for comments. Accordingly, the article has been retracted as the editors have lost confidence in the accuracy and integrity of the whole body of data and consider the conclusions of the article invalid. The authors were informed of the retraction decision but were unavailable for final confirmation.
RETRACTION: Ang II-AT1R Increases Cell Migration Through PI3K/AKT and NF-κB Pathways in Breast Cancer.
J Cell Physiol · 2026 Apr · PMID 41978542 · Publisher ↗
Y. Zhao, H. Wang, X. Li, M. Cao, H. Lu, Q. Meng, H. Pang, H. Li, C. Nadolny, X. Dong, and L. Cai, "Ang II-AT1R Increases Cell Migration Through PI3K/AKT and NF-κB Pathways in Breast Cancer," Journal of Cellular Physiolog...
Y. Zhao, H. Wang, X. Li, M. Cao, H. Lu, Q. Meng, H. Pang, H. Li, C. Nadolny, X. Dong, and L. Cai, "Ang II-AT1R Increases Cell Migration Through PI3K/AKT and NF-κB Pathways in Breast Cancer," Journal of Cellular Physiology 229, no. 11 (2014): 1855-1862, https://doi.org/10.1002/jcp.24639. The above article, published online on 01 April 2014 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors; the journal Editor-in-Chief, Robert Heath; and Wiley Periodicals LLC. The retraction has been agreed due to concerns raised by third parties. Image duplications have been identified within Figure 1a and across Figures 1a, 1b, 2 f, 3a, 3c, 3 d, 4a, and 4e. The scope of the corrections proposed by the authors extended beyond the panels implicated in the identified issues, thereby further undermining the editors' confidence in the accuracy and integrity of the whole body of work presented in the article. Accordingly, the article has been retracted, as the editors consider the conclusions to be invalid.
Role of Chitinase 3-like-1 in Myelofibrosis via Fibroblast-Produced Extracellular Matrix Enhancement.
Kato S, Kawamura T, Maekawa T … +4 more , Ogata H, Tachi N, Osawa Y, Kobayashi S
J Cell Physiol · 2026 Apr · PMID 41937713 · Full text
Cluster of differentiation 14 monocytes produced spindle-shaped fibrocytes, similar to fibroblasts. Recent studies have reported that fibrocytes are crucial for the development and progression of primary myelofibrosis (M...
Cluster of differentiation 14 monocytes produced spindle-shaped fibrocytes, similar to fibroblasts. Recent studies have reported that fibrocytes are crucial for the development and progression of primary myelofibrosis (MF); however, their functional role remains unclear. We compared monocytes and fibrocytes using RNA sequencing for gene expression profiles. We focused on chitinase 3-like-1 (CHI3L1), which causes inflammation, organ fibrosis, and extracellular tissue remodeling. We found higher CHI3L1 levels in patients with myeloproliferative neoplasm with MF than in those without MF. Further, serum CHI3L1 levels were significantly associated with the presence of MF and splenomegaly in patients with lymphoid tumors. Romiplostim-induced MF in a mouse model demonstrated extensive bone marrow (BM) CHI3L1 mRNA expression, which was reversed by clodronate treatment. Two MF induction experiments on CHI3L1 mice, based on romiplostim or Janus kinase 2 mutations, revealed fewer reticular fibers in silver-stained BM slices than in wild-type mice. A culture assay revealed that high CHI3L1 concentrations promoted extracellular matrix production by fibroblast cell lines, and that a CHI3L1-neutralizing antibody abrogated this effect. These results indicate the importance of CHI3L1 in the association between fibrocytes and fibroblasts in MF and could be a focus for future treatment.
Impact of Maternal Supraphysiological Hypercholesterolemia on Lysosomal and Mitochondrial Function in Placental Trophoblast Cells.
Yañez MJ, Campos F, Valdebenito P … +8 more , Cavieres VA, Barrera MJ, Tapia-Rojas C, Burgos PV, Monteiro LJ, Zanlungo S, Illanes SE, Leiva A
J Cell Physiol · 2026 Apr · PMID 41937698 · Publisher ↗
Dyslipidemia, characterized by an excessive amount of lipids in the bloodstream, is a significant risk factor for metabolic disorders and cardiovascular diseases (CVDs). Maternal supraphysiological hypercholesterolemia (...
Dyslipidemia, characterized by an excessive amount of lipids in the bloodstream, is a significant risk factor for metabolic disorders and cardiovascular diseases (CVDs). Maternal supraphysiological hypercholesterolemia (MSPH) is associated with increased maternal levels of total cholesterol (TC) and low-density lipoprotein (LDL). This condition has been linked to negative consequences on the fetoplacental vasculature, including increased atherosclerosis development in the fetal aorta and later in children and adolescents. This study aims to determine whether the high cholesterol levels associated with MSPH affect lysosomal and mitochondrial functions in the syncytiotrophoblast (STB), considering the increased free cholesterol levels previously reported in primary human trophoblast (PHT) cells from MSPH pregnancies. Total cholesterol levels were measured in placental tissues and BeWo cells. Lysosomal mass, size, and activity, as well as mitochondrial mass, function, and morphology, were assessed in BeWo cells and placentas. Our results revealed that placental tissues from MSPH pregnancies and BeWo cells treated with oxidized (ox-LDL) exhibited increased free cholesterol levels and higher expression of cholesterol transport proteins. Treatment of BeWo cells with ox-LDL also led to an increase in lysosomal mass and size, accompanied by a decrease in lysosomal activity. Conversely, ox-LDL treatment induced mitochondrial fragmentation in BeWo cells, together with reduced ATP production and diminished mitochondrial membrane potential. Similar alterations in lysosomes and mitochondria were observed in the placenta of patients with a history of MSPH. MSPH-related high cholesterol levels induced by ox-LDL impair lysosomal and mitochondrial functions in the STB, potentially contributing to cellular dysfunction observed in MSPH. This study highlights the importance of understanding the underlying mechanisms of MSPH to improve maternal and fetal health outcomes.
Innate Immune Receptor NLRX1: Potential Modulator of Glioblastoma Pathophysiology.
Meena D, Shivakumar D, Rajkhowa S … +9 more , Solanki P, Chhipa S, Bhattacharya N, Revanth MS, Kumar D, Janu V, Garg M, Gosal JS, Jha S
J Cell Physiol · 2026 Mar · PMID 41885462 · Publisher ↗
Gliomas are primary brain tumors that develop from glial cells within the central nervous system and are among the deadliest human cancers. Glioblastoma (GBM) is the most malignant form of glioma. NLRX1 is an innate immu...
Gliomas are primary brain tumors that develop from glial cells within the central nervous system and are among the deadliest human cancers. Glioblastoma (GBM) is the most malignant form of glioma. NLRX1 is an innate immune pattern recognition receptor that exhibits tumor-suppressive or tumor-promoting effects that may be cancer type- and context-dependent, aided by differences in the microenvironment. Here, we report that NLRX1 is differentially expressed in microglia, astrocytes, GBM cell lines, and glioma patient tissues. siRNA-mediated silencing of NLRX1 induces metabolic stress in GBM cells, as observed by an increased number of tunneling nanotubes (TNTs) formation between GBM cells and decreased expression of autophagy markers. Moreover, silencing of NLRX1 decreases the ability of the GBM cell lines, LN-229 and LN-18, to proliferate and migrate. si-NLRX1 GBM cells exhibit attenuated ability to generate 3D spheroids. In summary, our findings indicate that NLRX1 positively regulates GBM pathophysiology by supporting GBM cell metabolism, proliferation, migration, and anchorage-independent growth. We believe our understanding of NLRX1 in GBM pathophysiology paves the way for potential development of GBM-targeting therapeutics that may delay disease progression and/or improve survival.
The Laminin-Derived Peptide C16 Interacts With β1 Integrin, and Is Internalized by Vesicles Through Endocytic Pathway.
Galheigo MRU, Mateus RS, Cruz MC … +8 more , Nora OA, Smuczek B, Villarinho NJ, Bernardi JM, Juliano MA, Viana Pinheiro JJ, Freitas VM, Jaeger RG
J Cell Physiol · 2026 Mar · PMID 41883074 · Publisher ↗
Breast cancer is one of the leading causes of mortality worldwide. The tumor microenvironment plays a critical role in cancer progression. This microenvironment is composed of various cells embedded in the extracellular...
Breast cancer is one of the leading causes of mortality worldwide. The tumor microenvironment plays a critical role in cancer progression. This microenvironment is composed of various cells embedded in the extracellular matrix (ECM). Laminin-111, a major ECM glycoprotein, produces bioactive peptides that influence tumor biology. We have shown that the laminin-derived peptide C16 (KAFDITYVRLKF), located in the short arm of the γ1 chain, regulates migration, invasion, and invadopodia formation in different cancer cells. Our findings suggest that the regulatory mechanisms underlying the effects of C16 are associated with β1 integrin. This prompted us to investigate the interaction between the C16 peptide and β1 integrin in breast cancer cells. We found that breast cancer cells bind to C16 peptide, and this attachment is inhibited by β1 integrin depletion via siRNA. Cellular localization of the C16 peptide was analyzed using transmission electron microscopy (TEM) and time-lapse fluorescence microscopy. TEM revealed that nanogold-conjugated C16 decorated the cell membrane and was localized in intracellular vesicles, indicating peptide endocytosis. Time-lapse confocal microscopy showed that C16 was internalized by breast cancer cells within 2 h of incubation, with this process increasing over time. Based on these observations, we hypothesized that the peptide is endocytosed and directed to the endosome-lysosome pathway for degradation. Time-lapse imaging demonstrated that part of the internalized peptide colocalized with lysosomes in breast cancer cells. This suggests that C16 may be involved in integrin recycling. Furthermore, rhodamine-labeled C16 colocalized with activated β1 integrins. Flow cytometry analysis showed that C16 increased β1 integrin activation starting at 1 h of treatment. In summary, our results suggest that after interacting with the cell membrane and activating β1 integrins, breast cancer cells internalize peptide C16, which plays a role in β1 integrin turnover.
RETRACTION: Long Noncoding Ribonucleic Acid NKILA Induces the Endoplasmic Reticulum Stress/Autophagy Pathway and Inhibits the Nuclear Factor-k-Gene Binding Pathway in Rats After Intracerebral Hemorrhage.
J Cell Physiol · 2026 Mar · PMID 41883053 · Publisher ↗
J. Jia, M. Zhang, Q. Li, Q. Zhou, and Y. Jiang, "Long Noncoding Ribonucleic Acid NKILA Induces the Endoplasmic Reticulum Stress/Autophagy Pathway and Inhibits the Nuclear Factor-k-Gene Binding Pathway in Rats After Intra...
J. Jia, M. Zhang, Q. Li, Q. Zhou, and Y. Jiang, "Long Noncoding Ribonucleic Acid NKILA Induces the Endoplasmic Reticulum Stress/Autophagy Pathway and Inhibits the Nuclear Factor-k-Gene Binding Pathway in Rats After Intracerebral Hemorrhage" Journal of Cellular Physiology 233, no. 1 (2018): 8839-8849. https://doi.org/10.1002/jcp.26798. The above article, published online on 12 June 2018 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Robert Heath, and Wiley Periodicals LLC. A third party reported that all images in Figure 11 were duplicated within the same figure and that all images in Figure 3 were duplicated from other articles by different authors [Yu et al. 2016 (https://doi.org/10.18632/oncotarget.7492) and Cheng et al. 2018 (https://doi.org/10.1002/cam4.1276)]. An investigation by the publisher confirmed these duplications and also found that the beta-actin band in Figure 5B had been duplicated in a later article by different authors [Liu et al. 2019 (https://doi.org/10.1080/15384101.2020.1717041)]. The authors did not respond to an inquiry by the publisher. The retraction has been agreed to because the evidence of multiple image duplications both within the article and with other articles by different authors fundamentally compromises the editors' confidence in the results presented in this article.
Correction to "A Negative Feedback Loop of H19/miR-675/VDR Mediates Therapeutic Effect of Curcumin in the Treatment of Glioma".
J Cell Physiol · 2026 Mar · PMID 41879024 · Publisher ↗
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