J. Cell. Physiol. [JOURNAL]
Sun
200 papers
Loss of UCHL1 Leads to Enhanced Mouse Osteoclast Formation.
Chiba M, Hoshikawa S, Shimizu K … +6 more , Fujita H, Wada K, Yamada A, Saito K, Inuzuka H, Fukumoto S
J Cell Physiol · 2025 Apr · PMID 40227754 · Publisher ↗
Enhanced osteoclastogenesis causes bone fragility, osteoporosis, and an increased risk of fractures. Recent studies have suggested a possible correlation between osteoporosis and the pathological features of Parkinson's...
Enhanced osteoclastogenesis causes bone fragility, osteoporosis, and an increased risk of fractures. Recent studies have suggested a possible correlation between osteoporosis and the pathological features of Parkinson's disease (PD). To establish a molecular link between these conditions, we focused on the physiological function of the PD-related protein ubiquitin carboxy-terminal hydrolase L1 (UCHL1) in bone remodeling. To this end, we investigated the role of UCHL1 in regulating osteoclast differentiation in Uchl1 spontaneous mutant gad mice. We found that gad-mouse-derived osteoclast progenitors exhibit enhanced osteoclast differentiation. Likewise, CRISPR-mediated Uchl1 knockout in mouse macrophage-derived preosteoclast RAW-D cells increased RANKL-dependent osteoclastogenesis. Supporting this observation, these Uchl1-depleted cells showed elevated expression of osteoclast marker genes. To uncover the molecular mechanisms by which the loss of Uchl1 enhances osteoclast differentiation, we screened for UCHL1-interacting proteins in RAW-D preosteoclast cells and identified AKT1 as a potential UCHL1-regulated protein. UCHL1 depletion in preosteoclasts led to increased Thr308/Ser473 phosphorylation of AKT1. Furthermore, ectopic expression of UCHL1 decreased the K63-linked polyubiquitination of AKT1. These findings suggest that UCHL1 is critical in partially suppressing osteoclastogenesis through modulating AKT signaling.
Methods to Assess Neuronal Primary Cilia Electrochemical Signaling.
DeCaen PG, Kimura LF
J Cell Physiol · 2025 Apr · PMID 40227694 · Full text
Primary cilia are polymodal sensory organelles which project from the apical side of polarized cells. They are found in all brain hemispheres but are most pronounced in neurons, which comprise the granular layers of the...
Primary cilia are polymodal sensory organelles which project from the apical side of polarized cells. They are found in all brain hemispheres but are most pronounced in neurons, which comprise the granular layers of the hippocampus and cerebellum. Pathogenic variants in genes which encode primary cilia components are responsible for neuronal ciliopathies-a group of central nervous system disorders characterized by neurodevelopmental conditions such as intellectual disability, seizure, ataxia, and sensory deficits. In the hippocampus, neuronal primary cilia form chemical synapses with axons and their membranes are populated with unique sets of ion channels and G protein-coupled receptors (GPCRs). Primary cilia are small and privileged compartments that are challenging organelles to study. In detail, we describe cilia electrophysiology methods and the use of cilia-specific fluorescent sensors to assay neuronal polycystin channel function and serotonergic receptor signaling, respectively. These tools allow researchers to assay calcium, cAMP and channel-related signaling pathways in isolated neurons in real-time and in semi-quantitative terms, while enhancing our understanding of this understudied organelle and its dysregulation in ciliopathy disease states.
Correction to "Beta-Arrestin 2 Mediates Cardiac Hypertrophy Induced by Thyroid Hormones via AT1R".
J Cell Physiol · 2025 Apr · PMID 40213894 · Publisher ↗
Abstract loading — click title to view on PubMed.
Mesenchymal Stem Cell Treatment for Peripheral Nerve Injuries.
Wu Y, Lu R, Yin H … +3 more , Peng D, Pan R, Lv L
J Cell Physiol · 2025 Apr · PMID 40211799 · Publisher ↗
Peripheral nerve injuries (PNI) affect hundreds of thousands of patients annually, often leading to life-altering consequences such as significant impairments in motor function and sensory perception. In recent years, a...
Peripheral nerve injuries (PNI) affect hundreds of thousands of patients annually, often leading to life-altering consequences such as significant impairments in motor function and sensory perception. In recent years, a growing body of evidence indicates that mesenchymal stem cell (MSC) treatment could complement traditional treatment and improve therapeutic outcomes for these injuries. This paper reviews emerging insights into the potential benefits of MSC treatment for PNI and summarizes selected examples of the interactions between MSCs, peripheral nerves, and their microenvironment, which have advanced our understanding of the pathophysiology of MSC-based therapy. We believe that this rapidly moving field holds great promise for future advancements, guiding the rational design of safe and effective treatments for patients with PNI.
RETRACTION: Porphyromonas Gingivalis and Dental Stem Cells Crosstalk Amplify Inflammation and Bone Loss in the Periodontitis Niche.
J Cell Physiol · 2025 Apr · PMID 40177800 · Publisher ↗
D. Ezhilarasan, and S. S. Varghese, "Porphyromonas Gingivalis and Dental Stem Cells Crosstalk Amplify Inflammation and Bone Loss in the Periodontitis Niche," Journal of Cellular Physiology 237, no. 10 (2022): 3768-3777,...
D. Ezhilarasan, and S. S. Varghese, "Porphyromonas Gingivalis and Dental Stem Cells Crosstalk Amplify Inflammation and Bone Loss in the Periodontitis Niche," Journal of Cellular Physiology 237, no. 10 (2022): 3768-3777, https://doi.org/10.1002/jcp.30848. The above article, published online on 4 August 2022 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Robert Heath; and Wiley Periodicals LLC. Following publication, it has come to the attention of the journal that the article was accepted solely on the basis of compromised peer review processes. Therefore, the decision to retract this article was taken. The authors have been informed of the decision of retraction and disagree with it.
Pleiotropic Role of TNIK in Sepsis-Induced Cardiomyopathy.
Yang W, Zhao A, Lei W … +5 more , Chen J, Yan H, Li J, Yang Y, Chen Y
J Cell Physiol · 2025 Apr · PMID 40176540 · Publisher ↗
Heart failure induced by sepsis is considered one of the foremost contributors to mortality in intensive care unit (ICU) patients. However, the molecular mechanism of myocardial damage in sepsis has not been fully elucid...
Heart failure induced by sepsis is considered one of the foremost contributors to mortality in intensive care unit (ICU) patients. However, the molecular mechanism of myocardial damage in sepsis has not been fully elucidated at present. TNF receptor-associated factor-2 and Nck-interacting protein kinase (TNIK) are members of the germinal center kinase superfamily. TNIK exhibits a pivotal role as a conserved modulator of glucose and lipid homeostasis. Here, we aimed to investigate the potential direct roles of TNIK and whether TNIK exerts anti-septic myocardial damage by regulating the NLRP3 pathway. We initially revealed that TNIK was the crucial involvement of septic myocardial injury. Subsequently, we constructed a cecal ligation and puncture (CLP) mouse model and employed LPS-induced injury in HL-1 cardiomyocytes. Our observations revealed an upregulation of TNIK levels in both CLP-injured mice and LPS-treated HL-1 cells. However, TNIK inhibitor TNIK-IN-7 or siRNA attenuated cardiomyocyte LPS injury. Especially, TNIK siRNA can significantly downregulate TNIK as well as decrease NLRP3 and IL-1β mRNA and protein levels, though the explicit molecular mechanisms of TNIK-NLRP3 in septic myocardial require further investigation. Together, our investigation presents novel evidence suggesting TNIK as a potential therapeutic target for the prevention and therapeutic intervention in sepsis-induced cardiomyopathy.
RETRACTION: Phytosomal Curcumin Inhibits Tumor Growth in Colitis-Associated Colorectal Cancer.
J Cell Physiol · 2025 Apr · PMID 40171833 · Publisher ↗
R. M. Marjaneh, F. Rahmani, S. M. Hassanian, N. Rezaei, M. Hashemzehi, A. Bahrami, F. Ariakia, H. Fiuji, A. Sahebkar, A. Avan, and M. Khazaei, "Phytosomal Curcumin Inhibits Tumor Growth in Colitis-Associated Colorectal C...
R. M. Marjaneh, F. Rahmani, S. M. Hassanian, N. Rezaei, M. Hashemzehi, A. Bahrami, F. Ariakia, H. Fiuji, A. Sahebkar, A. Avan, and M. Khazaei, "Phytosomal Curcumin Inhibits Tumor Growth in Colitis-Associated Colorectal Cancer," Journal of Cellular Physiology 233, no. 10 (2018): 6785-6798, https://doi.org/10.1002/jcp.26538. The above article, published online on 8 May 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 on the data presented in the article. Specifically, evidence of inappropriate post-acquisition image editing, including splicing sites have been detected in Figure 6a. Furthermore, no correspondence between sections at lower and higher magnification was found for the "AOM", "5-FU", and "Curcumin" groups in Figure 4e and f. The authors were unable to retrieve the original data underlying the Western Blot experiments presented in Figure 6a due to the time elapsed since performing the experiments. Additionally, original data provided for Figure 4 was insufficient to resolve the issues. Accordingly, the article is retracted as the editors have lost confidence in the accuracy and integrity of the whole body of data presented in the article and consider its conclusions invalid. The authors have been informed of the decision of retraction.
SLO2.1/NALCN Functional Complex Activity in Mouse Myometrial Smooth Muscle Cells During Pregnancy.
Ferreira JJ, Kent LN, McCarthy R … +9 more , Butler A, Ma X, Peramsetty N, Amazu C, Zhang A, Whitter GC, Li E, England SK, Santi CM
J Cell Physiol · 2025 Apr · PMID 40170408 · Full text
At the end of pregnancy, the uterus transitions from a quiescent to a highly contractile state. This is partly due to the depolarization of the resting membrane potential in uterine (myometrial) smooth muscle cells (MSMC...
At the end of pregnancy, the uterus transitions from a quiescent to a highly contractile state. This is partly due to the depolarization of the resting membrane potential in uterine (myometrial) smooth muscle cells (MSMCs). In human MSMCs, the membrane potential is regulated by a functional complex between the sodium (Na)-activated potassium (K) channel SLO2.1 and the Na leak channel nonselective (NALCN). Na entering through NALCN activates SLO2.1, leading to K efflux, membrane hyperpolarization (cells become more negative inside), and reduced contractility. Decreased SLO2.1/NALCN activity results in reduced K efflux, leading to membrane depolarization, Ca influx via voltage-dependent calcium channels, and increased MSMC contractility. However, all of these data are from MSMCs isolated from women at term, so the role of the SLO2.1/NALCN complex early in pregnancy was speculative. To address this question here, we examined the role of the SLO2.1/NALCN complex in regulating mouse MSMC membrane potential across pregnancy. We report that Slo2.1 and Nalcn are more highly expressed in MSMCs from nonpregnant and early pregnant mice than in those from late-pregnant mice. Functional studies revealed that SLO2.1 channels mediate a significant portion of the K current in mouse MSMCs, particularly in cells from nonpregnant and early pregnant mice. Activation of SLO2.1 by Na influx through NALCN led to membrane hyperpolarization in MSMCs from early pregnancy but not in MSMCs from later pregnancy. Moreover, the NALCN/SLO2.1 complex regulates intracellular Ca responses more in MSMCs from nonpregnant and early pregnancy mice than in MSMCs from late pregnancy. Together, these findings reveal that the SLO2.1/NALCN functional complex is conserved between mice and humans and functions throughout pregnancy. This study could open avenues for targeted pharmacological interventions for pregnancy-related complications.
The Thromboxane Levels in Ovarian Follicular Fluid Are Inversely Correlated With Oocyte Maturation: Implications of PAR-2/-3 Cooperation and Thromboxane Participation in Follicle Development.
Chen HT, Lai TH, Lin JJ … +2 more , Chen CC, Wu WB
J Cell Physiol · 2025 Apr · PMID 40170403 · Publisher ↗
It has been reported the presence of components from the coagulation thrombin-generating pathway and prostaglandins (PGs) in human ovarian follicular fluid (FF) but with unclear functions. Moreover, thrombin can induce C...
It has been reported the presence of components from the coagulation thrombin-generating pathway and prostaglandins (PGs) in human ovarian follicular fluid (FF) but with unclear functions. Moreover, thrombin can induce COX-2 expression linking to PG synthesis in several cell types. Therefore, this study sought to explore the thromboxane (TX) generation in FF and the correlation between FF TX levels and oocyte maturation. The FF TXB (a stable metabolite of TXA) levels exhibited a negative correlation between large preovulatory leading and small mid-antral follicles from in vitro fertilization (IVF) patients, indicating a requirement of TX for a small follicle/oocyte to grow/mature. Further receiver operating characteristic curve analysis identified that intrafollicular TXB level could predict oocyte maturity. Thrombin was found expressed in a similar pattern/trend to TXB in intrafolliclar FF, where it could induce TXB production/secretion in human ovarian follicular GCs via proteinase-activated receptor-2 (PAR-2) and PAR-3 cooperation/transactivation and Erk/p38 MAPK/JNK signaling to cause COX-2/TXB induction. Accordingly, PAR-2 and -3 were present in human ovarian follicular GCs and thrombin, PAR-2 agonist, and TXA analog caused a substantial enhancement in follicle development, which could be blocked by the PAR-2, COX-2, and TXA prostanoid (TP) receptor inhibitors in an ex vivo cultured murine ovary model. Collectively, we first demonstrated that FF thrombin regulates PAR-2/-3 cooperation and MAPK signaling pathways to induce COX-2 expression and TX production in follicular GCs, possibly supporting intrafollicular TX levels and triggering TP-related pathways to enhance follicle development. The FF TX levels also can be a predictor for oocyte maturation during IVF.
RETRACTION: DUSP1 Recuses Diabetic Nephropathy via Repressing JNK-Mff-Mitochondrial Fission Pathways.
J Cell Physiol · 2025 Mar · PMID 40145126 · Publisher ↗
Sheng, J., H. Li, Q. Dai, C. Lu, M. Xu, J. Zhang, and J. Feng, "DUSP1 Recuses Diabetic Nephropathy via Repressing JNK-Mff-Mitochondrial Fission Pathways." Journal of Cellular Physiology 234, no. 3 (2019): 3043-3057. http...
Sheng, J., H. Li, Q. Dai, C. Lu, M. Xu, J. Zhang, and J. Feng, "DUSP1 Recuses Diabetic Nephropathy via Repressing JNK-Mff-Mitochondrial Fission Pathways." Journal of Cellular Physiology 234, no. 3 (2019): 3043-3057. https://doi.org/10.1002/jcp.27124. The above article, published online on September 7, 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. Several irregularities were found, including, but not limited to, multiple image elements being published in later articles by different author groups and in distinct scientific contexts, indicating inappropriate data sharing. The authors were invited to comment on these concerns but did not respond. Further investigation by the publisher revealed that the article was accepted solely on the basis of a compromised peer review process. Accordingly, the article is retracted as the editors have lost confidence in the integrity and reliability of the full body of data presented in the article and consider its conclusions invalid. The authors were informed of the retraction.
SMC2 and Condensin II Subunits Are Essential for the Development of Hematopoietic Stem and Progenitor Cells in Zebrafish.
Oh CK, Kim MS, Shin U … +11 more , Kang JW, Kim YH, Ko HS, Ra JS, Ahn S, Choi EY, Yu S, Nam U, Choi T, Myung K, Lee Y
J Cell Physiol · 2025 Mar · PMID 40134128 · Full text
Hematopoietic stem and progenitor cells (HSPCs) play a pivotal role in blood cell production, maintaining the health and homeostasis of individuals. Dysregulation of HSPC function can lead to blood-related diseases, incl...
Hematopoietic stem and progenitor cells (HSPCs) play a pivotal role in blood cell production, maintaining the health and homeostasis of individuals. Dysregulation of HSPC function can lead to blood-related diseases, including cancer. Despite its importance, our understanding of the genes and pathways underlying HSPC development and the associated pathological mechanisms remains limited. To elucidate these unknown mechanisms, we analyzed databases of patients with blood disorders and performed functional gene studies using zebrafish. We employed bioinformatics tools to explore three public databases focusing on patients with myelodysplastic syndrome (MDS) and related model studies. This analysis identified significant alterations in several genes, especially SMC2 and other condensin-related genes, in patients with MDS. To further investigate the role of Smc2 in hematopoiesis, we generated smc2 loss-of-function zebrafish mutants using CRISPR mutagenesis. Further analyses of the mutants revealed that smc2 depletion induced G2/M cell cycle arrest in HSPCs, leading to their maintenance and expansion failure. Notably, although the condensin II subunits (ncaph2, ncapg2, and ncapd3) were essential for HSPC maintenance, the condensin I subunits did not affect HSPC development. These findings emphasize the crucial role of condensin II in ensuring healthy hematopoiesis via promoting HSPC proliferation.
Cardiomyocytic FoxP3 Attenuates Expression of β Isoform of Myosin Heavy Chain During Cardiac Hypertrophy and Effects of Triptolide.
Hong JH, Pan XC, Xiong YL … +4 more , Wang P, Yuan Y, Liu Y, Zhang HG
J Cell Physiol · 2025 Mar · PMID 40123330 · Publisher ↗
Cardiac hypertrophy, a maladaptive response to chronic stress, progresses to heart failure through mechanisms requiring deeper exploration. While forkhead helix transcription factor P3 (FoxP3) is well-known as a key regu...
Cardiac hypertrophy, a maladaptive response to chronic stress, progresses to heart failure through mechanisms requiring deeper exploration. While forkhead helix transcription factor P3 (FoxP3) is well-known as a key regulator in CD4 T cells, its role in cardiomyocytes remains unclear. Here, by using isoproterenol (ISO)-induced cardiac hypertrophy models (40 mg/kg daily for in vivo study and 10 μmol/L for in vitro study), we revealed the protective role of FoxP3 in cardiac hypertrophy. Though modulating FoxP3 expression using siRNA or plasmid in cardiomyocytes, we found that FoxP3 knockdown exacerbated ISO-induced hypertrophic responses, while overexpression of FoxP3 attenuated hypertrophic effects. The protective function of cardiomyocytic FoxP3 in vivo was further confirmed by infection of adeno-associated virus. Mechanically, the cardiomyocytic FoxP3 decreased the expression of nuclear factor of activated T cells c3 (NFATc3), a key regulator of hypertrophy-related genes, to suppress hypertrophy-related genes, including atrial natriuretic peptide, brain natriuretic peptide and β-myosin heavy chain (β-MHC), and thus ameliorate hypertrophic responses. Besides, the immunoprecipitation and immunofluorescence determination showed that FoxP3 could interact with NFATc3 in the nucleus to form a transcription complex, thereby regulating the transcription activity of NFATc3. Chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assays (EMSAs) revealed the specific binding sequences of FoxP3 in the β-MHC promoter region, with binding occupancy reduced by ISO, suggesting that FoxP3 could interact with NFATc3 to down-regulate the β-MHC expression. Importantly, we identified triptolide (TP), a bioactive natural product, as a potent inducer of FoxP3 expression. Both in vivo (10 μg/kg daily) and in vitro (10 μmol/L) studies demonstrated that TP significantly reversed cardiac hypertrophy by upregulating FoxP3 expression, thereby inhibiting NFATc3-mediated β-MHC transcription. These findings highlight cardiomyocytic FoxP3 as a novel protective factor, elucidating its underlying mechanisms and demonstrating the therapeutic potential of TP in this process.
Daytime-Restricted Feeding Alleviates D-Galactose-Induced Aging in Mice and Regulates the AMPK and mTORC1 Activities.
Li T, Huang N, Chen H … +9 more , Yang Y, Zhang J, Xu W, Gong H, Gong C, Yang M, Zhao T, Wang F, Xiao H
J Cell Physiol · 2025 Mar · PMID 40070151 · Publisher ↗
Time-restricted feeding (TRF) is a distinct regimen of intermittent fasting advocated for health improving. Although nighttime TRF (NRF) in rodents is analogous to daytime TRF (DRF) in humans and has health benefits, the...
Time-restricted feeding (TRF) is a distinct regimen of intermittent fasting advocated for health improving. Although nighttime TRF (NRF) in rodents is analogous to daytime TRF (DRF) in humans and has health benefits, the effects of DRF on rodent's health remain uncertain. The adverse health effects of DRF in rodents are primarily attributed to its implementation-induced temporal shift in the expression of circadian rhythm-related genes. However, studies also demonstrate the health-beneficial effect of restricted feeding itself on metabolic homeostasis, particularly in periphery tissues. Moreover, the direct effects of DRF on aging progression in rodents are underexplored, highlighting a gap in current research. To explore the overall health effects of long-term DRF in rodents, especially its influence on aging progression, we investigated the impact of long-term DRF on mice under a progeric aging condition. Results showed that both 4-h and 8-h DRF regimens exerted positive effects on aging retardation; these effects were manifested as improved physical and memory capacities, enhanced liver and kidney functions, and reduced oxidative damage and inflammatory response. These DRF regimens also lowered the manifestation of aging-related markers in peripheral tissues, with decreased SA-β-gal staining and p16 expression. Mechanistically, DRF regimens, especially DRF8, upregulated AMPK signaling and downregulated mTORC1 signaling. Interestingly, the health benefits of DRF are similar to those of metformin intervention. In conclusion, our study demonstrates for the first time that DRF effectively counteracts oxidative stress-induced aging progression in mice, supporting the viewpoint that TRF as a promising strategy for preventing aging and aging-related disorders.
Corrigendum to "The Effects and Mechanisms of Myeloid Differentiation Protein 2 on Intestinal Mucosal Permeability in Mice With Chronic Colitis".
J Cell Physiol · 2025 Feb · PMID 40008420 · Publisher ↗
Abstract loading — click title to view on PubMed.
Comparative Single-Cell Analysis Reveals Tendon Progenitor Dysfunction by Age-Associated Oxidative Stress and Its Restoration by Antioxidant Treatments.
Jeong Y, Yang D, Solidum JG … +2 more , Ortinau L, Park D
J Cell Physiol · 2025 Feb · PMID 39987523 · Full text
Impaired healing of adult tendons with fibrosis remains clinical challenges while neonatal tendons have full functional restoration. However, age-associated cellular and molecular changes in tendon cells and tendon stem/...
Impaired healing of adult tendons with fibrosis remains clinical challenges while neonatal tendons have full functional restoration. However, age-associated cellular and molecular changes in tendon cells and tendon stem/progenitor cells (TSPCs) remain unknown. Here, comparative single cell transcriptomics of early postnatal (2 weeks old) and adult (20 weeks old) mouse tendons revealed that adult tendons have reduced number of TSPCs, decreased gene expression in tendon and cartilage development, and a greater population of fibro-tenogenic cells. Notably, adult TSPCs and tenocytes exhibit increased expression of immune-response and oxidative-stress genes with higher EGFR but decreased IGF signaling. Adult tendon cells show increased levels of intracellular reactive oxygen species (ROS) in vivo. In contrast, antioxidant treatment of adult tendons significantly reduces intracellular ROS of TSPCs and improves tendon strength in vivo. Hence, these findings suggest that increased inflammation and ROS during tendon aging deteriorates tendon function and regeneration that can be mitigated by antioxidant treatment.
Trophic Factors in Muscle-Nerve Cross-Talk Signaling Augment Muscle Fiber and Motor Endplate Development.
Redden JT, Kothe S, Cohen DJ … +2 more , Schwartz Z, McClure MJ
J Cell Physiol · 2025 Feb · PMID 39987522 · Publisher ↗
Synaptogenesis requires complex coordination between the terminating motor neuron and the developing myofiber endplate. Cross-talk research has focused on in vivo models or singular treatments with known signaling molecu...
Synaptogenesis requires complex coordination between the terminating motor neuron and the developing myofiber endplate. Cross-talk research has focused on in vivo models or singular treatments with known signaling molecules identified from these animal studies. However, in vivo models are inefficient at measuring dynamic signaling changes due to assay resolution and cost. Further, despite advances in culture methods relying on microfluidic platforms, much remains unknown about the dynamic cross-talk between these two key cell types. As such, there is an unmet investigation into simple and reproducible coculture studies. In this study, we characterize both myoblast (C2C12) and motor neuron (NSC-34) changes that occur in either a conditioned media model, a transwell coculture, and a 2D migration coculture. We successfully demonstrate repeatable changes in synaptogenesis with ~38% increase in Chrng protein levels (p < 0.05) in each model, increased myotube alignment in cocultured myoblasts measured with FFT analysis, and show motor neurons are preferentially chemo-attracted to myotubes without the use of neurite-path constraining microfluidics. Lastly, we identified a potential new signaling protein responsible for motor endplate development, apolipoprotein E (ApoE). This coculture approach reveals changes to myotube myogenesis and synaptogenesis providing a consistent platform for cross-talk and pathway analysis for future studies.
Role of Metabolic Sensor GPR81/HCAR1 in Diabetic Podocytes: Downregulated Lipolysis Results in the Deterioration of Glomerular Filtration Barrier.
Grochowalska K, Szrejder M, Rachubik P … +4 more , Audzeyenka I, Rogacka D, Narajczyk M, Piwkowska A
J Cell Physiol · 2025 Feb · PMID 39962919 · Publisher ↗
The effacement of podocyte foot processes, which form slit diaphragms, are common features of proteinuria. Exploring podocyte energy metabolism, especially under diabetic conditions, may offer insights into the pathogene...
The effacement of podocyte foot processes, which form slit diaphragms, are common features of proteinuria. Exploring podocyte energy metabolism, especially under diabetic conditions, may offer insights into the pathogenesis of diabetic kidney disease. Lipid accumulation is recognized as a cause of podocyte cytoskeleton remodeling and insulin resistance. Thus, the role of the metabolic sensor G-protein-coupled receptor 81 (GPR81) was examined in the molecular pathway of lipid accumulation in podocytes under hyperglycemic conditions. It was discovered that hyperglycemia downregulated the cyclic adenosine monophosphate/protein kinase A signaling pathway, which downregulated the expression of adipose triglyceride lipase (ATGL). Perilipin 1 was also downregulated; simultaneously, lipid droplet accumulation was enhanced. Glycerol and free fatty acid concentrations were also reduced, providing evidence of lipolysis inhibition. Interestingly, the expression of GPR81 decreased under hyperglycemia conditions despite the evidence of its activation, indicating strict lipolysis regulation. More importantly, cell functions were altered, reflected by an increase in albumin permeability and rearrangement of the actin cytoskeleton. The effect of ATGL activity inhibition on lipolysis, actin cytoskeleton arrangement, and permeability of the podocyte monolayer was investigated. The results were similar to GPR81 downregulation. Altogether, the present data indicate that GPR81 is likely a crucial part of the lipid sensing system, and its alterations during hyperglycemia might contribute to glomerular filtration barrier deterioration in diabetic kidney disease.
Single-Cell Transcriptome Decoding Umbilical Cord-Derived Mesenchymal Stem Cell Heterogeneity Reveals a Unique IL1R1PDGFRA Ultroser-G-MSC With Osteogenesis and Chondrogenesis Signatures.
Huang S, Xu X, Guo J … +8 more , Li Z, Wu Y, Liu Y, Sun Q, Wang S, Yan H, Su Y, Guo W
J Cell Physiol · 2025 Feb · PMID 39956958 · Publisher ↗
The heterogeneity of human umbilical cord mesenchymal stem cells (hUC-MSCs) is culturing-dependent, resulting in functional non-uniformness. To achieve the best clinical benefit, a comprehensive understanding of the orig...
The heterogeneity of human umbilical cord mesenchymal stem cells (hUC-MSCs) is culturing-dependent, resulting in functional non-uniformness. To achieve the best clinical benefit, a comprehensive understanding of the origin of the heterogeneity in different culture systems can identify functional subgroups to direct the precise application of hUC-MSCs. Here, we create a single-cell transcriptome atlas of hUC-MSC in different culture systems for the identification of a subgroup of Ultroser-G-MSCs with high osteogenic and chondrogenic potentials featured by high expressions of IL1R1 and PDGFRA. Further experimental validations surprisingly reveal that IL1R1PDGFRA Ultroser-G-MSCs possess advantages over "traditional" hUC-MSCs in the treatments of modeled osteoarthritis, leading to a cell-cell communication network centered in Clusters 0 and 2. Moreover, we found that Wnt5 signaling is the key pathway for the dynamic transformation of osteogenic and chondrogenic phenotypes in hUC-MSC. Overall, the present study paves the way for the clarification of heterogenetic nature of hUC-MSC in different culture systems for the selection of optimal MSC types to achieve the precision on clinical treatments.
Stearoyl-CoA Desaturase 1 Regulates Metabolism and Inflammation in Mouse Perivascular Adipose Tissue in Response to a High-Fat Diet.
Sowka A, Balatskyi VV, Navrulin VO … +2 more , Ntambi JM, Dobrzyn P
J Cell Physiol · 2025 Feb · PMID 39943782 · Publisher ↗
The dysregulation of perivascular adipose tissue (PVAT) is a key contributor to obesity-induced vascular dysfunction. Mouse periaortic adipose tissue is divided into two parts: thoracic perivascular adipose tissue (TPVAT...
The dysregulation of perivascular adipose tissue (PVAT) is a key contributor to obesity-induced vascular dysfunction. Mouse periaortic adipose tissue is divided into two parts: thoracic perivascular adipose tissue (TPVAT) and abdominal perivascular adipose tissue (APVAT). These two parts have different physiological properties, which translate into different effects on the vascular wall in the onset of metabolic syndrome. Stearoyl-CoA desaturase 1 (SCD1) is an enzyme that is involved in the synthesis of monounsaturated fatty acids and has been shown to play an important role in metabolic syndrome, including vascular homeostasis. Despite a considerable focus on the role of SCD1 in the development of vascular disorders, there is currently a lack of knowledge of the relationship between SCD1 and PVAT. The present study investigated effects of SCD1 deficiency on lipolysis, β-oxidation, mitochondrial dynamics, and inflammation in mouse TPVAT and APVAT under high-fat diet (HFD) feeding conditions. We found lower triglyceride levels in PVAT in SCD1 mice both in vitro and in vivo compared with wildtype perivascular adipocytes, attributable to activated lipolysis and β-oxidation. Moreover, PVAT in HFD-fed SCD1 mice was characterized by higher levels of oxidative phosphorylation complexes and mitochondrial respiratory potential and alterations of mitochondrial morphology compared with wildtype mice. Furthermore, TPVAT and APVAT in SCD1 mice showed signs of greater pro-inflammatory macrophage polarization and higher inflammatory markers that were induced by a HFD. This may be related to the accumulation free fatty acids and diacylglycerols, which are enriched in saturated fatty acids. These findings elucidate the role of SCD1 in maintaining vascular integrity.
Molecular Mechanisms and Therapeutic Implications of Long Non-coding RNAs in Cutaneous Biology and Disease.
Zuccotti A, Al-Fatyan F, Ferretti GDS … +5 more , Bertolini I, Long DT, Sahin O, Rodriguez-Blanco J, Barnoud T
J Cell Physiol · 2025 Feb · PMID 39943735 · Full text
Human skin is the largest organ of the human body and accounts for approximately fifteen percent of the total bodyweight. Its main physiological role is to protect the body against a wide range of environmental factors i...
Human skin is the largest organ of the human body and accounts for approximately fifteen percent of the total bodyweight. Its main physiological role is to protect the body against a wide range of environmental factors including pathogens, ultraviolet light, and injury. Importantly, the skin can regenerate and heal upon injury in large part by the differentiation of keratinocytes. Not surprisingly, dysregulation of cutaneous differentiation and self-renewal can result in a variety of skin-related pathologies, including autoimmune disease and cancer. Increasing evidence supports the premise that long non-coding RNAs (lncRNAs) act as critical mediators of gene expression and regulate important biological processes within the skin. Notably, dysregulation of lncRNAs has been shown to influence diverse physiological and pathological consequences. More recently, numerous reports have revealed new mechanistic insight on the role that lncRNAs play in skin homeostasis as well as their contribution to the pathogenesis of skin-related disorders. Here, we review the biological functions of cutaneous lncRNAs and their impact on skin homeostasis. We also describe the fundamental roles of lncRNAs in the pathogenesis of skin-related disorders, including fibrotic, autoimmune, and malignant diseases. Lastly, we will highlight how a better understanding of lncRNAs at the molecular level may reveal novel therapeutic approaches for the improvement of cutaneous disorders.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe