J. Cell. Physiol. [JOURNAL]
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200 papers
Proarrhythmic Lipid Inflammatory Mediators: Mechanisms in Obesity Arrhythmias.
Bahrami P, Aromolaran KA, Aromolaran AS
J Cell Physiol · 2025 Feb · PMID 39943721 · Full text
The prevalence of obesity and associated metabolic disorders such as diabetes is rapidly increasing; therefore, concerns regarding their cardiovascular consequences, including cardiac arrhythmias, are rising. As obesity...
The prevalence of obesity and associated metabolic disorders such as diabetes is rapidly increasing; therefore, concerns regarding their cardiovascular consequences, including cardiac arrhythmias, are rising. As obesity progresses, the excessively produced lipids accumulate in unconventional areas such as the epicardial adipose tissue (EAT) around the myocardium. Metabolic alterations in obesity contribute to the transformation of these ectopic fat deposits into arrhythmogenic substrates. However, despite advances in therapeutic approaches, particularly in lowering EAT volume and thickness through sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, obese and diabetic patients still suffer from fatal arrhythmias that may lead to sudden cardiac death. Therefore, an investigation into how unappreciated underlying pathways such as lipid mediators contribute to the transformation of adipose tissues into proinflammatory and arrhythmogenic substrates is of significance. Leukotriene B4 (LTB4) is an eicosanoid derived from arachidonic acid and acts as a lipid mediator. LTB4 has recently been identified to be associated with cardiac ion channel modulations and arrhythmogenic conditions in diabetes. LTB4 increases circulatory free fatty acids (FFAs) and has been associated with adipocyte hypertrophy. LTB4 also interferes with insulin signaling pathways, instigating insulin resistance (IR). In addition, LTB4, as a potent chemoattractant, contributes to the mobilization of circulatory immune cells such as monocytes and promotes inflammatory macrophage polarization and macrophage dysfunction. Thus, this review provides a comprehensive overview of LTB4's underlying pathways in obesity; illustrates how these pathways might lead to alterations in cardiac ion channels, currents, and cardiac arrhythmias; and shows how they might pose a therapeutic target for metabolic-associated arrhythmias.
Correction to "Effects of Photoperiod on Morphology and Function in Testis and Epididymis of Cricetulus Barabensis".
J Cell Physiol · 2025 Feb · PMID 39943710 · Publisher ↗
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Unraveling pH Regulation of TMEM175, an Endolysosomal Cation Channel With a Role in Parkinson's Disease.
Schulze T, Rauh O, Thiel G … +3 more , Fertig N, Bazzone A, Grimm C
J Cell Physiol · 2025 Feb · PMID 39902728 · Full text
Transmembrane protein 175 (TMEM175) is an endolysosomal cation channel, which has attracted much attention recently from academics and the pharmaceutical industry alike since human mutations in TMEM175 were found to be a...
Transmembrane protein 175 (TMEM175) is an endolysosomal cation channel, which has attracted much attention recently from academics and the pharmaceutical industry alike since human mutations in TMEM175 were found to be associated with the development of Parkinson's disease (PD). Thus, gain-of-function mutations were identified, which reduce and loss-of-function mutations, which increase the risk of developing PD. After having been characterized as an endolysosomal potassium channel initially, soon after TMEM175 was claimed to act as a proton channel. In fact, recent evidence suggests that depending on the conditions, TMEM175 can act as either a potassium or proton channel, without acting as an antiporter or exchanger. A recent work has now identified amino acid H57 to be directly involved in gating, increasing proton conductance of the channel while leaving the potassium conductance unaffected. We review here the current knowledge of TMEM175 function, pharmacology, physiology, and pathophysiology. We discuss the potential of this ion channel as a novel drug target for the treatment of neurodegenerative diseases such as PD, and we discuss the discovery of H57 as proton sensor.
Carboxyl Terminal Modulator Protein Induces Cell Senescence and Is Upregulated With Aging by Zic2 in Rats.
Shan W, Li J, Philpot Z … +1 more , Zuo Z
J Cell Physiol · 2025 Jan · PMID 39888066 · Full text
Carboxyl terminal modulator protein (CTMP) may be involved in various physiological and pathological processes, such as inflammation, tumor growth, and cardiac hypertrophy. Our recent study has shown that CTMP is increas...
Carboxyl terminal modulator protein (CTMP) may be involved in various physiological and pathological processes, such as inflammation, tumor growth, and cardiac hypertrophy. Our recent study has shown that CTMP is increased with aging and plays a role in determining brain ischemic tolerance. However, it is not known how CTMP expression with aging is regulated and whether the changed CTMP expression has an effect on cell senescence. Here, cells that stably overexpressed CTMP were generated and cell senescence biomarkers were determined. The brains of Fischer 344 male rats were harvested for Western blot analysis and immunostaining to detect CTMP and the Zinc finger protein Zic2. The regulations of CTMP expression by Zic2 were examined by promoter activity assays. Increasing CTMP enhanced cells expressing senescence-associated β-galactosidase staining but without expression of Ki67, decreased cell proliferation and colony formation, and increased cells with condensed DNA of more than one pair of homologous chromosomes caused by senescence. Zic2 was decreased with aging in rats. Zic2 and CTMP were mainly expressed in the neurons in rats. Similarly, CTMP protein was expressed in the neurons of human brain. An anti-Zic2 antibody immunoprecipitated DNA fragments of ctmp gene. Zic2 inhibited the activity of presumptive ctmp promoter. Overexpressing Zic2 decreased CTMP in cells. These results suggest that CTMP induces cell senescence and that Zic2 is a suppressor of CTMP expression. The decrease of Zic2 contributes to CTMP increase with aging.
Rho GTPase Signaling: A Molecular Switchboard for Regulating the Actin Cytoskeleton in Axon Guidance.
Gorla M, Guleria DS
J Cell Physiol · 2025 Jan · PMID 39888031 · Publisher ↗
Axon pathfinding is a highly dynamic process regulated by the interactions between cell-surface guidance receptors and guidance cues present in the extracellular environment. During development, precise axon pathfinding...
Axon pathfinding is a highly dynamic process regulated by the interactions between cell-surface guidance receptors and guidance cues present in the extracellular environment. During development, precise axon pathfinding is crucial for the formation of functional neural circuits. The spatiotemporal expression of axon guidance receptors helps the navigating axon make correct decisions in a complex environment comprising both attractive and repulsive guidance cues. Axon guidance receptors initiate distinct signaling cascades that eventually influence the cytoskeleton at the growing tip of an axon, called the growth cone. The actin cytoskeleton is the primary target of these guidance signals and plays a key role in growth cone motility, exploration, and behavior. Of the many regulatory molecules that modulate the actin cytoskeleton in response to distinct guidance signals, Rho GTPases play central roles. Rho GTPases are molecular switchboards; their ON (GTP-bound) and OFF (GDP-bound) switches are controlled by their interactions with proteins that regulate the exchange of GDP for GTP or with the proteins that promote GTP hydrolysis. Various upstream signals, including axon guidance signals, regulate the activity of these Rho GTPase switch regulators. As cycling molecular switches, Rho GTPases interact with and control the activities of downstream effectors, which directly influence actin reorganization in a context-dependent manner. A deeper exploration of the spatiotemporal dynamics of Rho GTPase signaling and the molecular basis of their involvement in regulating growth cone actin cytoskeleton can unlock promising therapeutic strategies for neurodevelopmental disorders linked to dysregulated Rho GTPase signaling. This review not only provides a comprehensive overview of the field but also highlights recent discoveries that have considerably advanced our understanding of the complex regulatory roles of Rho GTPases in modulating actin cytoskeleton arrangement at the growth cone during axon guidance.
RETRACTION: Promotion of Cell Autophagy and Apoptosis in Cervical Cancer by Inhibition of Long Noncoding RNA LINC00511 via Transcription Factor RXRA-regulated PLD1.
J Cell Physiol · 2025 Jan · PMID 39888011 · Publisher ↗
Y. Shi, M. Liu, Y. Huang, J. Zhang, and L. Yin, "Promotion of Cell Autophagy and Apoptosis in Cervical Cancer by Inhibition of Long Noncoding RNA LINC00511 via Transcription Factor RXRA-regulated PLD1," Journal of Cellul...
Y. Shi, M. Liu, Y. Huang, J. Zhang, and L. Yin, "Promotion of Cell Autophagy and Apoptosis in Cervical Cancer by Inhibition of Long Noncoding RNA LINC00511 via Transcription Factor RXRA-regulated PLD1," Journal of Cellular Physiology 235, no. 10 (2020): 6592-6604. https://doi.org/10.1002/jcp.29529. The above article, published online on 17 February 2020 in Wiley Online Library (wileyonlinelibrary.com), and has been retracted by agreement between the journal Editor-in-Chief, Robert Heath; and Wiley Periodicals LLC. A third party reported that images shared overlapping sections in Figure 5D in this article, and this duplication was confirmed by the publisher. The third party also reported that the tumor measurement ruler used in Figure 5 A is identical to the ruler used in the figures of previously published articles from different authors, each of which describes a different scientific context (Chen, et al. 2019 [https://doi.org/10.1002/jcp.28911]) and (Feng, et al. 2019 [https://doi.org/10.1186/s13287-022-02841-z]). The use of the identical ruler in the figures of different articles from unrelated research groups at different institutions puts in doubt the veracity of the data reported. The authors did not respond to an inquiry by the publisher. The retraction has been agreed on because the evidence of image duplication within this article, as well as unexplained duplication of image elements and equipment with other experiments by different authors, fundamentally compromises the conclusions reported in this article. The authors did not respond to our notice regarding the retraction.
RETRACTION: Role of Mirnas in Lung Cancer.
J Cell Physiol · 2025 Jan · PMID 39887974 · Publisher ↗
A. Uddin and S. Chakraborty, "Role of miRNAs in Lung Cancer," Journal of Cellular Physiology (Early View), https://doi.org/10.1002/jcp.26607. The above article, published online on 20 April 2018 in Wiley Online Library (...
A. Uddin and S. Chakraborty, "Role of miRNAs in Lung Cancer," Journal of Cellular Physiology (Early View), https://doi.org/10.1002/jcp.26607. The above article, published online on 20 April 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 upon following an investigation into concerns raised by a third party, which revealed major textual overlap between this article and two previously published articles by different groups of authors elsewhere (Guz et al. 2014; Hubaux 2012). The authors noted the major textual overlap and revised their manuscript during the proofing stage, yet the wrong version of the manuscript was published in Early View by mistake. The editors and the publisher apologize for this oversight. During the investigation, the authors were able to provide their revised article, however, also the revised version shows high textual and conceptual similarity to the two previously published review articles (Guz et al. 2014; Hubaux 2012). The authors disagree with the retraction. References Guz, M., A. Rivero-Müller, E. Okoń, et al. 2014. "Micrornas-Role in Lung Cancer." Disease Markers 2014, no. 1: 1-13. https://doi.org/10.1155/2014/218169. Hubaux, R. 2012. "Micrornas as Biomarkers for Clinical Features of Lung Cancer." Journal of Postgenomics: Drug & Biomarker Development 2, no. 3: 1000108. https://doi.org/10.4172/2153-0769.1000108.
Corrigendum to "Defining Early Hematopoietic-Fated Primitive Streak Specification of Human Pluripotent Stem Cells by the Orchestrated Balance of Wnt, Activin, and BMP Signaling".
J Cell Physiol · 2025 Jan · PMID 39865952 · Publisher ↗
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Corrigendum to "Immortalized Hertwig's Epithelial Root Sheath Cell Line Works as a Model for Epithelial-Mesenchymal Interaction During Tooth Root Formation".
J Cell Physiol · 2025 Jan · PMID 39865781 · Publisher ↗
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Single-Cell Transcriptomic Analysis Reveals Biomechanical Loading-Induced Imbalance in Bone and Fat, Leading to Ossification in Lumbar Intervertebral Disc Nucleus Pulposus Degeneration.
Zhang P, Wang Y, Bai J … +5 more , Zhang J, Zhang S, Guo X, Zhan J, Zhu L
J Cell Physiol · 2025 Jan · PMID 39854079 · Publisher ↗
In this study, we explored the impact of different biomechanical loadings on lumbar spine motion segments, particularly concerning intervertebral disc degeneration (IVDD). We aimed to uncover the cellular milieu and mech...
In this study, we explored the impact of different biomechanical loadings on lumbar spine motion segments, particularly concerning intervertebral disc degeneration (IVDD). We aimed to uncover the cellular milieu and mechanisms driving ossification in the nucleus pulposus (NP) during IVDD, a process whose underlying mechanisms have remained elusive. The study involved the examination of fresh NP tissue from the L3-S1 segment of five individuals, either with IVDD or healthy. The analysis consisted of histopathological evaluation and single-cell RNA sequencing. To further validate the impact of biomechanical loading on IVDD, particularly on the CITED4 + METRN + NP chondrocytes and the bone-fat balance mechanism, a retrospective analysis was conducted using paraffin-embedded NP samples from patients. A distinct subset of CITED4 + METRN+ chondrocytes in the degenerated NP that were influenced by biomechanical loading was identified. These cells were evaluated for their potential as diagnostic biomarkers. Pseudotemporal analysis indicated that inflammation and repair processes were integral to NP ossification. Notably, the L4/5 and L5/S1 segments with severe IVDD showed pronounced ossification and heightened lipogenic metabolism. Cell communication analysis sheds light on the roles of bone-fat balance proteins and various ossification genes. Additionally, immunohistochemistry and immunofluorescence confirmed that biomechanical loading intensified IVDD by fostering osteogenic differentiation, mediated by macrophage migration inhibitory factor (MIF)-regulated bone-fat balance. This research reveals the microenvironmental factors of IVDD NP ossification under biomechanical loading, highlighting the role of bone-fat imbalance. These insights significantly enhance the understanding of IVDD pathogenesis and pave the way for innovative therapeutic approaches.
Reprogramming of Fatty Acid Metabolism in Acute Leukemia.
Sokei J, Kanefsky J, Sykes SM
J Cell Physiol · 2025 Jan · PMID 39835485 · Publisher ↗
Fatty acids are essential biomolecules that support several cellular processes, such as membrane structures, energy storage and production, as well as signal transduction. Accordingly, changes in fatty acid metabolism ca...
Fatty acids are essential biomolecules that support several cellular processes, such as membrane structures, energy storage and production, as well as signal transduction. Accordingly, changes in fatty acid metabolism can have a significant impact on cell behavior, such as growth, survival, proliferation, differentiation, and motility. Therefore, it is not surprising that many aspects of fatty acid metabolism are frequently dysregulated in human cancer, including in highly aggressive blood cancers such as acute leukemia. The aims of this review are to summarize the aspects of fatty acid metabolism that are specifically coopted in acute leukemia as well as current preclinical strategies for targeting fatty acid metabolism in these cancers.
CD44/Integrin β1 Association Drives Fast Motility on Hyaluronic Acid Substrates.
Roy T, Dutta S, Ghosh S … +2 more , Sthanam LK, Sen S
J Cell Physiol · 2025 Jan · PMID 39835458 · Publisher ↗
In addition to proteins such as collagen (Col) and fibronectin, the extracellular matrix (ECM) is enriched with bulky proteoglycan molecules such as hyaluronic acid (HA). However, how ECM proteins and proteoglycans colle...
In addition to proteins such as collagen (Col) and fibronectin, the extracellular matrix (ECM) is enriched with bulky proteoglycan molecules such as hyaluronic acid (HA). However, how ECM proteins and proteoglycans collectively regulate cellular processes has not been adequately explored. Here, we address this question by studying cytoskeletal and focal adhesion organization and dynamics on cells cultured on polyacrylamide hydrogels functionalized with Col, HA and a combination of Col and HA (Col/HA). We show that fastest migration on HA substrates is attributed to the presence of smaller and weaker focal adhesions. Integrin 1 co-localization and its association with CD44-which is the receptor for HA, and insensitivity of cell spreading to RGD on HA substrates suggests that focal adhesions on HA substrates are formed via integrin association with HA bound CD44. Consistent with this, adhesion formation and cell motility were inhibited when CD44 was knocked out. Collectively, our results suggest that association of integrin 1 with CD44 drives fast motility on HA substrates.
Glucose Transporter 1 Deficiency Impairs Glucose Metabolism and Barrier Induction in Human Induced Pluripotent Stem Cell-Derived Astrocytes.
Pervaiz I, Mehta Y, Al-Ahmad AJ
J Cell Physiol · 2025 Jan · PMID 39807611 · Publisher ↗
Glucose is a major source of energy for the brain. At the blood-brain barrier (BBB), glucose uptake is facilitated by glucose transporter 1 (GLUT1). GLUT1 Deficiency Syndrome (GLUT1DS), a haploinsufficiency affecting SLC...
Glucose is a major source of energy for the brain. At the blood-brain barrier (BBB), glucose uptake is facilitated by glucose transporter 1 (GLUT1). GLUT1 Deficiency Syndrome (GLUT1DS), a haploinsufficiency affecting SLC2A1, reduces glucose brain uptake. A lot of effort has been made to characterize GLUT1DS at the BBB, but the impact on astrocytes remains unclear. In this study, we investigated the impact of GLUT1DS on astrocyte differentiation and function in vitro, using human induced pluripotent stem cells GLUT1DS (GLUT1DS-iPSCs) differentiated into astrocyte-like cells (iAstros). GLUT1 expression is decreased during the differentiation of iPSCs into astrocytes, with neural progenitor cells showing the lowest expression. The presence of a truncated GLUT1 did not compromise the differentiation of iPSCs into iAstros, as these cells could express several key markers representative of the astrocyte lineage. GLUT1DS-iAstros failed to express full-length GLUT1 at protein levels while showing no signs of impaired GLUT4 expression. However, GLUT1DS-iAstros showed decreased glucose uptake and lactate production compared to control-iAstros, reduced glycolysis, and mitochondrial activity as well as ATP deficit. In addition to reduced energy production, astrocytes displayed a reduced extracellular glutamate release. As previously observed, one iAstros clone (C7) showed the most severe phenotype from all groups. Our study provides an insightful view of the contribution of GLUT1 in astrocytes' energetic metabolism and raises the possible contribution of these cells in the astrocyte-neuron metabolic coupling. Our future direction is to understand better how GLUT1DS impacts astrocytes and neurons within their metabolic coupling.
RETRACTION: MiR-145 Promotes MiR-133b Expression Through c-myc and DNMT3A-mediated Methylation in Ovarian Cancer Cells.
J Cell Physiol · 2025 Jan · PMID 39806777 · Publisher ↗
J. Li, S. Zhang, Y. Zou, L. Wu, M. Pei, and Y. Jiang, "MiR-145 Promotes MiR-133b Expression Through c-myc and DNMT3A-mediated Methylation in Ovarian Cancer Cells," Journal of Cellular Physiology 235, no. 5 (2020): 4291-4...
J. Li, S. Zhang, Y. Zou, L. Wu, M. Pei, and Y. Jiang, "MiR-145 Promotes MiR-133b Expression Through c-myc and DNMT3A-mediated Methylation in Ovarian Cancer Cells," Journal of Cellular Physiology 235, no. 5 (2020): 4291-4301, https://doi.org/10.1002/jcp.29306. The above article, published online on 14 October 2019 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Roberth Heath; and Wiley Periodicals LLC. The retraction has been agreed due to concerns raised by third parties on the data presented in the article. Specifically, instances of duplicated image elements were identified in Figures 2 d, 3 d, and 5 g. Therefore, the article is retracted as the editors consider its conclusions to be invalid. The authors have been informed of the decision of retraction.
RETRACTION: Long Noncoding RNA LINC00958 Regulates Cell Sensitivity to Radiotherapy Through RRM2 by Binding to microRNA-5095 in Cervical Cancer.
J Cell Physiol · 2025 Jan · PMID 39801448 · Publisher ↗
H. Zhao, G.-H. Zheng, G.-C. Li, L. Xin, Y.-S. Wang, Y. Chen, and X.-M. Zheng, "Long Noncoding RNA LINC00958 Regulates Cell Sensitivity to Radiotherapy Through RRM2 by Binding to microRNA-5095 in Cervical Cancer," Journal...
H. Zhao, G.-H. Zheng, G.-C. Li, L. Xin, Y.-S. Wang, Y. Chen, and X.-M. Zheng, "Long Noncoding RNA LINC00958 Regulates Cell Sensitivity to Radiotherapy Through RRM2 by Binding to microRNA-5095 in Cervical Cancer," Journal of Cellular Physiology 234, no. 12 (2019): 23349-23359. https://doi.org/10.1002/jcp.28902. The above article, published online on 06 June 2019 in Wiley Online Library (wileyonlinelibrary.com), and has been retracted by agreement between the journal Editor-in-Chief, Robert Heath; and Wiley Periodicals LLC. A third party reported that the same tumor image was detected between Figure 6 A in this article and Figure 7B in another article (Guo, et al. 2019 [https://doi.org/10.18632/aging.102271]. The third party reported additional image duplications between Figure 2B in this article and other articles by different authors (Guo, et al. 2018 [https://doi.org/10.1186/s12964-018-0290-6]; (Liu, et al. 2019 [https://doi.org/10.1002/jcp.27893]; (Wen, et al. 2019 [https://doi.org/10.1096/fj.201900310 R]; and (Ou, et al. 2020 [https://doi.org/10.1016/j.ebiom.2020.102694]. Each mentioned article describes a different scientific context. The authors did not respond to an inquiry by the publisher. The retraction has been agreed on because the evidence of image duplication with other articles fundamentally compromises the conclusions reported in this article. The authors did not respond to our notice regarding the retraction.
RETRACTION: Long Noncoding RNA LEF1-AS1 Silencing Suppresses the Initiation and Development of Prostate Cancer by Acting as a Molecular Sponge of miR-330-5p via LEF1 Repression.
J Cell Physiol · 2025 Jan · PMID 39801438 · Publisher ↗
D.-C. Liu, L.-L. Song, Q. Liang, L. Hao, Z.-G. Zhang, and C.-H. Han, "Long Noncoding RNA LEF1-AS1 Silencing Suppresses the Initiation and Development of Prostate Cancer by Acting as a Molecular Sponge of miR-330-5p via L...
D.-C. Liu, L.-L. Song, Q. Liang, L. Hao, Z.-G. Zhang, and C.-H. Han, "Long Noncoding RNA LEF1-AS1 Silencing Suppresses the Initiation and Development of Prostate Cancer by Acting as a Molecular Sponge of miR-330-5p via LEF1 Repression," Journal of Cellular Physiology 234, no. 8 (2019): 12727-12744. https://doi.org/10.1002/jcp.27893. The above article, published online on 05 January 2019 in Wiley Online Library (wileyonlinelibrary.com), and has been retracted by agreement between the journal Editor-in-Chief, Robert Heath; and Wiley Periodicals LLC. A third party reported that images shared overlapping sections in Figure 3B in this article, and this duplication was confirmed by the publisher. The third party also reported that duplicated images in this article had been detected in subsequent articles by different authors, each of which describes different experimental conditions (Zhao, et al. 2019 [https://doi.org/10.1002/jcp.28902]); (Ou, et al. 2020 [https://doi.org/10.1016/j.ebiom.2020.102694]; and (Sha, et al. 2021 [https://doi.org/10.18632/aging.203088]). The authors did not respond to an inquiry by the publisher. The retraction has been agreed on because the evidence of image duplication within this article, as well as subsequent unexplained duplications with other articles, fundamentally compromises the conclusions reported in this article. The authors responded to our notice regarding the retraction but did not state their agreement nor their disagreement with the retraction.
High Glucose Inhibits O-GlcNAc Transferase Translocation in Early Osteoblast Differentiation by Altering Protein Phosphatase 2A Activity.
Sitosari H, Fukuhara Y, Weng Y … +5 more , Zheng Y, He Y, Zheng X, Ikegame M, Okamura H
J Cell Physiol · 2025 Jan · PMID 39800889 · Publisher ↗
Our previous study revealed a link between O-GlcNAc transferase (OGT) localization and protein phosphatase 2A (PP2A) activity in osteoblast. Given the association of PP2A downregulation with osteoblast differentiation, w...
Our previous study revealed a link between O-GlcNAc transferase (OGT) localization and protein phosphatase 2A (PP2A) activity in osteoblast. Given the association of PP2A downregulation with osteoblast differentiation, we hypothesized that OGT localization changes during this process. We examined OGT localization in MC3T3-E1 cells undergoing differentiation under normal and high glucose conditions. Changes in PP2A activity were followed by alterations in OGT localization. Organ culture of calvaria revealed similar OGT localization changes in bone-surrounding osteoblasts near the suture area. Furthermore, the levels of O-GlcNAc modification in various proteins including Runt-related transcription factor 2, Osterix, and ATP synthase subunit alpha (ATP5A) were shifted in parallel with OGT translocation. These findings suggest a regulatory role of OGT, under the influence of PP2A, during osteoblast differentiation.
SMAD4 Regulates the Expression of LCK Affecting Chimeric Antigen Receptor-T Cells Proliferation Through PI3K/Akt Signaling Pathway.
Wan R, Fu B, Fu X … +6 more , Liu Z, Simayi N, Fu Y, Liang H, Li C, Huang W
J Cell Physiol · 2025 Jan · PMID 39763264 · Full text
The proliferation of CAR-T cells was hindered and cannot play its killing function well in solid tumors. And yet the regulatory mechanism of CAR-T cell proliferation is not fully understood. Here, we showed that recombin...
The proliferation of CAR-T cells was hindered and cannot play its killing function well in solid tumors. And yet the regulatory mechanism of CAR-T cell proliferation is not fully understood. Here, we showed that recombinant expression of CD19CAR in T cells significantly increased the basal activation level of CAR-T cells and LCK activation. Both LCK and SMAD4 were essential for CAR-T cells proliferation since over-express LCK or SMAD4 significantly promotes CAR-T cells proliferation, while knock-down LCK or SMAD4 expression inhibited the proliferation of CAR-T cells seriously. More cells go into apoptosis when knock-down LCK or SMAD4 expression, and the cell cycle was arrested in G2/M or S phase, respectively. Over-express LCK or SMAD4 significantly promotes phosphorylation of PI3K and Akt, while it was inhibited when cells were treated with PI3K and Akt inhibitors (LY294002 or MK2206). Further mechanism exploration experiments showed that SMAD4 bound on the promoter region of LCK regulating its expression. Taken together, we reported that the transcription factor SMAD4 regulated the expression of LCK and further involved in the PI3K/Akt signaling pathway to affect the proliferation of CAR-T cells.
Point of No Return-What Is the Threshold of Mitochondria With Permeability Transition in Cells to Trigger Cell Death.
Kritskaya KA, Stelmashchuk OA, Abramov AY
J Cell Physiol · 2025 Jan · PMID 39760157 · Full text
Programmed cell death (apoptosis) is essential part of the process of tissue regeneration that also plays role in the mechanism of pathology. The phenomenon of fast and transient permeability of mitochondrial membranes b...
Programmed cell death (apoptosis) is essential part of the process of tissue regeneration that also plays role in the mechanism of pathology. The phenomenon of fast and transient permeability of mitochondrial membranes by various triggers, known as permeability transition pore (mPTP) leads to the release of proapoptotic proteins and acts as an initial step in initiation of apoptosis. However, a role for mPTP was also suggested for physiology and it is unclear if there is a threshold in number of mitochondria with mPTP which induces cell death and how this mechanism is regulated in different tissues. Using simultaneous measurements of mitochondrial membrane potential and a fluorescent marker for caspase-3 activation we studied the number of mitochondria with calcium-induced mPTP opening necessary for induction of apoptosis in rat primary cortical neurons, astrocytes, fibroblasts, and cancer (BT-474) cells. The induction of apoptosis was correlated with 80%-90% mitochondrial signal loss in neural cells but only 35% in fibroblasts, and in BT-474 cancer cells over 90% of mitochondria opens mPTP before apoptosis becomes obvious. The number of mitochondria with mPTP which induce cell death did not correlate with total expression levels of proapoptotic proteins but was consistent with the Bax/Bcl-2 ratio in these cells. Calcium-induced mPTP opening increased levels of necrosis which was higher in fibroblasts compared to neurons, astrocytes and BT-474 cells. Thus, different tissues require specific numbers of mitochondria with PTP opening to induce apoptosis and it correlates to the proapoptotic/antiapoptotic proteins expression ratio in them.
Physiological Insights Into the Role of Pericytes in Spinal Cord Injury.
Jin H, Rawlins J, Chen Y … +9 more , Zheng X, Charlesworth O, Chen J, Wang G, Luo H, Cheng W, Li ZA, Zhu S, Xu J
J Cell Physiol · 2025 Jan · PMID 39757951 · Full text
Vascular regeneration plays a vital role in tissue repair yet is drastically impaired in those with a spinal cord injury (SCI). Pericytes are of great significance as they are entwined with vessel-specific endothelial ce...
Vascular regeneration plays a vital role in tissue repair yet is drastically impaired in those with a spinal cord injury (SCI). Pericytes are of great significance as they are entwined with vessel-specific endothelial cells and actively contribute to maintaining the spinal cord's vascular network. Within the neurovascular unit (NVU), subtypes of pericytes characterized by various markers such as PDGFR-β, Desmin, CD146, and NG-2 are involved in vascular regeneration in SCI repair. Various pericyte signaling, pericyte-derived exosomes, and endothelial-pericyte interplay were revealed to participate in SCI repair or fibrotic scars. Through further understanding pericyte biology, it is aimed to accurately generate subtypes of pericytes and develop their therapeutic potential. This review focuses on recent advanced research and development of pericytes as a potential treatment for SCI.
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