Journal of Cellular Physiology最新文献

{"title":"CBLB Regulates MAPK-P38 Pathway via MAP3K9 Ubiquitination to Inhibit GBM Cell Invasion and Migration","authors":"Yuankun Liu,&nbsp;Kaixiang Ni,&nbsp;Songyun Zhao,&nbsp;Jingjing Zhao,&nbsp;Mengmeng Zhong,&nbsp;Chao Cheng,&nbsp;Wei Ji,&nbsp;Jiantong Jiao,&nbsp;Junfei Shao","doi":"10.1002/jcp.70037","DOIUrl":"https://doi.org/10.1002/jcp.70037","url":null,"abstract":"<div>\u0000 \u0000 <p>Glioma cells exhibit high invasiveness and have the ability to evade surgical resection, radiotherapy, and chemotherapy, which are major factors contributing to the challenges in effective treatment and recurrence. The ubiquitin-proteasome system (UPS) plays a crucial role in posttranslational modification, significantly contributing to the aggressive progression of glioblastoma (GBM). This study identified the E3 ubiquitin ligase CBLB as a crucial and abnormally regulated component of the UPS in GBM, noting its significant downregulation compared to normal brain tissue and its negative correlation with malignant phenotypes and poor prognosis. Experimental studies, both in vitro and in vivo, have shown that CBLB can inhibit the migration and invasion of GBM cells. Mechanistically, CBLB directly interacts with MAP3K9 through its RING domain, leading to K48-K63-linked polyubiquitination at the Lys 193 site, thereby promoting MAP3K9 proteasomal-mediated degradation. MAP3K9 downregulation suppresses MAPK-P38 pathway activation. This study identifies CBLB as a tumor suppressor that modulates the MAPK-P38 signaling pathway by promoting the polyubiquitination and degradation of MAP3K9, offering a new therapeutic approach for GBM treatment.</p></div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143852872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EXPRESSION OF CONCERN: EW-7197 Prevents Ulcerative Colitis-Associated Fibrosis and Inflammation","authors":"","doi":"10.1002/jcp.70028","DOIUrl":"https://doi.org/10.1002/jcp.70028","url":null,"abstract":"<p><b>EXPRESSION OF CONCERN</b>: M. M. Binabaj, F. Asgharzadeh, A. Avan, F. Rahmani, A. Soleimani, M. R. Parizadeh, et al., “EW-7197 Prevents Ulcerative Colitis-Associated Fibrosis and Inflammation,” <i>Journal of Cellular Physiology</i> 234, no. 7 (2018): 11654-11661, https://doi.org/10.1002/jcp.27823.</p><p>This Expression of Concern is for the above article, published online on 27 November 2018 in Wiley Online Library (wileyonlinelibrary.com), and has been published by agreement between the journal Editor-in-Chief, Robert Heath; and Wiley Periodicals LLC. The Expression of Concern has been agreed due to concerns raised by the third party, which revealed inappropriate figure overlap in Figure 2(a), by the similar group of authors in different articles. While the corresponding author provided original data during the investigation, the reproduced control and colitis data (Figure 2a) are indeed considered unreliable as they were published elsewhere in a different scientific context. However, the authors have explained they conducted these experiments of the murine model of colitis using mice with the uniform characteristics including their age, species, and gender. More importantly, these experiments were conducted simultaneously by the same researchers in the same location, with the same molecular weight DSS, contributing to the consistency in the patterns observed. Furthermore, the Chair, Research Integrity Committee of the institution (Mashhad University of Medical Sciences, Mashhad, Iran) has contacted the journal and confirmed that this article was a thesis independently conducted with different research aims, methodologies, and datasets in their university. Nevertheless, the Editor-in-Chief and the Publisher's Research Integrity team have decided to publish this Expression of Concern to inform readers that concerns about the reliability of the presented results remain.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.70028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “SMAD4 Regulates the Expression of LCK Affecting Chimeric Antigen Receptor-T Cells Proliferation Through PI3K/Akt Signaling Pathway”","authors":"","doi":"10.1002/jcp.70039","DOIUrl":"https://doi.org/10.1002/jcp.70039","url":null,"abstract":"<p>Wan, R., Fu, B., Fu, X., et al. 2025. “SMAD4 Regulates the Expression of LCK Affecting Chimeric Antigen Receptor-T Cells Proliferation Through PI3K/Akt Signaling Pathway.” <i>Journal of Cellular Physiology</i> 240, no. 1: e31520.</p><p>In the author list part of the paper, Rongxue Wan and Bowen Fu are co-first authors who contributed equally to the paper, however, there was no sign to reflect this, which was incorrect. To correct, the sentence “Rongxue Wan and Bowen Fu contributed equally to this study” should be added under the author list part.</p><p>We apologize for this error.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.70039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143845917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copper Impedes Calcification of Human Aortic Vascular Smooth Muscle Cells Through Inhibition of Osteogenic Transdifferentiation and Promotion of Extracellular Matrix Stability","authors":"Iurii Orlov,&nbsp;Gaëlle Lenglet,&nbsp;Carine Avondo,&nbsp;John H. Beattie,&nbsp;Said Kamel,&nbsp;Irina Korichneva","doi":"10.1002/jcp.70035","DOIUrl":"https://doi.org/10.1002/jcp.70035","url":null,"abstract":"<p>Vascular calcification (VC), a common pathological condition, is a strong predictor of cardiovascular events and associated mortality. Development and progression of VC heavily rely on vascular smooth muscle cells (VSMCs) and are closely related to oxidative stress, inflammation, and remodelling of extracellular matrix (ECM). Copper (Cu), an essential microelement, participates in these processes, but its involvement in pathophysiology of VC and VSMCs physiology remains poorly investigated. In the present study, we analysed the impact of Cu on the calcification of human aortic primary VSMCs induced in vitro by treatment with high calcium and phosphate levels. Supplementation with physiological micromolar doses of Cu significantly reduced the amount of calcium deposited on VSMCs as compared to moderate deficiency, Cu restriction with chelators or Cu excess. Moreover, optimal concentrations of Cu ions increased protein production by VSMCs, stimulated their metabolic activity, inhibited alkaline phosphatase activity associated with cell-conditioned medium and cellular lysates, and prevented osteogenic differentiation of VSMCs. RNA-seq results indicated that high calcium and phosphate treatments activated many pathways related to oxidative stress and inflammation in VSMCs at the initial stage of calcification. At the same time, expression of VSMCs-specific markers and certain components of ECM were downregulated. Supplementation of calcifying cells with 10 μM Cu prevented most of the transcriptomic alterations induced by high calcium and phosphate while chelation-mediated restriction of Cu greatly aggravated them. In summary, physiological concentration of Cu impedes in vitro calcification of VSMCs, prevents their osteogenic transition and minimises early phenotypic alterations induced by high calcium and phosphate, thereby underlining the importance of Cu homeostasis for the physiology of VSMCs, one of the cornerstones of cardiovascular health. Our data suggest that features of Cu metabolism and its status should be considered when developing preventive and therapeutic approaches for cardiovascular diseases.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143845916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Piezo1 Is Related to the Enamel Matrix Formation in Mouse Tooth Germ Development","authors":"Hiroko Wada,&nbsp;Misaki Abe,&nbsp;Naohisa Wada,&nbsp;Shohei Yoshimoto,&nbsp;Shinsuke Fujii,&nbsp;Masafumi Moriyama,&nbsp;Yoshihide Mori,&nbsp;Mizuho A. Kido,&nbsp;Tamotsu Kiyoshima","doi":"10.1002/jcp.70036","DOIUrl":"https://doi.org/10.1002/jcp.70036","url":null,"abstract":"<div>\u0000 \u0000 <p>Cellular responses to mechanical stimulation are involved in tissue development and the maintenance of biological functions. Teeth function as receptors for mastication and occlusal pressure. During tooth development, the tooth germ begins with an invagination of the epithelium, and its morphology matures through dynamic interactions between epithelial cells and mesenchymal cells, suggesting that mechanosensors may play an important role in this process. We analyzed the expression and function of Piezo1, a mechanically activated ion channel, during tooth development and clarified the involvement of Piezo1 in tooth morphogenesis. The expression of Piezo1 was observed in both the enamel organ and the surrounding mesenchymal cells at the early stage and in the ameloblasts and odontoblasts during enamel and dentin matrix formation. Yoda1, a Piezo1 activator, inhibited cell proliferation in mouse dental epithelial (mDE6) cells and E15 tooth germs, and suppressed cell migration in mDE6 cells. Meanwhile, GsMTx4, a Piezo1 inactivator, showed opposite results. Furthermore, in the organ culture of E15 tooth germs, the activation and inactivation of Piezo1 were found to affect the expression of ameloblast differentiation marker genes and control the arrangement of ameloblasts. Interestingly, the expression of E-cadherin was reduced in the cell membrane of ameloblasts at the cusp in the GsMTx4-treated tooth germs of organ culture, and enamel formation was significantly decreased. Yoda1-treated mDE6 cells showed upregulated E-cadherin expression, which was downregulated by calpain inhibitor. These findings suggest that Piezo1 may be involved in tooth morphogenesis during ameloblast development by playing an essential role in cell proliferation, migration, arrangement, differentiation, and mineralization.</p></div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143836467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methods to Assess Neuronal Primary Cilia Electrochemical Signaling","authors":"Paul G. DeCaen,&nbsp;Louise F. Kimura","doi":"10.1002/jcp.70034","DOIUrl":"https://doi.org/10.1002/jcp.70034","url":null,"abstract":"<p>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.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.70034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of MCUB-Dependent Inhibition of Mitochondrial Calcium Uptake","authors":"Neeraj K. Rai,&nbsp;David R. Eberhardt,&nbsp;Anthony M. Balynas,&nbsp;Melissa J. S. MacEwen,&nbsp;Ashley R. Bratt,&nbsp;Yasemin Sancak,&nbsp;Dipayan Chaudhuri","doi":"10.1002/jcp.70033","DOIUrl":"https://doi.org/10.1002/jcp.70033","url":null,"abstract":"<p>Mitochondrial Ca²⁺ levels are regulated to balance stimulating respiration against the harm of Ca²⁺ overload. Contributing to this balance, the main channel transporting Ca²⁺ into the matrix, the mitochondrial Ca²⁺ uniporter, can incorporate a dominant-negative subunit (MCUB). MCUB is homologous to the pore-forming subunit MCU, but when present in the pore-lining tetramer, inhibits Ca²⁺ transport. Here, using cell lines deleted of both MCU and MCUB, we identify three factors that contribute to MCUB-dependent inhibition. First, MCUB protein requires MCU to express. The effect is mediated via the N-terminal domain (NTD) of MCUB. Replacement of the MCUB NTD with the MCU NTD recovers autonomous expression but fails to rescue Ca²⁺ uptake. Surprisingly, mutations to MCUB that affect interactions with accessory subunits or the conduction pore all failed to rescue Ca²⁺ uptake, suggesting the mechanism of inhibition may involve more global domain rearrangements. Second, using concatemeric tetramers with varying MCU:MCUB ratios, we find that MCUB incorporation does not abolish conduction, but rather inhibits Ca²⁺ influx proportional to the amount of MCUB present in the channel. Reducing rather than abolishing Ca²⁺ transport is consistent with MCUB retaining the highly-conserved selectivity filter DIME sequence. Finally, we apply live-cell Förster resonance energy transfer to establish that the endogenous stoichiometry is 2:2 MCU:MCUB. Taken together, our results suggest MCUB preferentially incorporates into nascent uniporters, and the amount of MCUB protein present linearly correlates with the degree of inhibition of Ca²⁺ transport, creating a precise, tunable mechanism for cells to regulate mitochondrial Ca²⁺ uptake.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of UCHL1 Leads to Enhanced Mouse Osteoclast Formation","authors":"Mitsuki Chiba,&nbsp;Seira Hoshikawa,&nbsp;Kouhei Shimizu,&nbsp;Hiromi Fujita,&nbsp;Keiji Wada,&nbsp;Aya Yamada,&nbsp;Kan Saito,&nbsp;Hiroyuki Inuzuka,&nbsp;Satoshi Fukumoto","doi":"10.1002/jcp.70032","DOIUrl":"https://doi.org/10.1002/jcp.70032","url":null,"abstract":"<div>\u0000 \u0000 <p>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 <i>Uchl1</i> spontaneous mutant <i>gad</i> mice. We found that <i>gad-</i>mouse-derived osteoclast progenitors exhibit enhanced osteoclast differentiation. Likewise, CRISPR-mediated <i>Uchl1</i> knockout in mouse macrophage-derived preosteoclast RAW-D cells increased RANKL-dependent osteoclastogenesis. Supporting this observation, these <i>Uchl1</i>-depleted cells showed elevated expression of osteoclast marker genes. To uncover the molecular mechanisms by which the loss of <i>Uchl1</i> 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.</p></div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143831117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal Stem Cell Treatment for Peripheral Nerve Injuries","authors":"Yue Wu,&nbsp;Ruijie Lu,&nbsp;Hongtao Yin,&nbsp;Deqing Peng,&nbsp;Ruolang Pan,&nbsp;Liangzhong Lv","doi":"10.1002/jcp.70031","DOIUrl":"https://doi.org/10.1002/jcp.70031","url":null,"abstract":"<div>\u0000 \u0000 <p>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.</p></div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143818419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Beta-Arrestin 2 Mediates Cardiac Hypertrophy Induced by Thyroid Hormones via AT1R”","authors":"","doi":"10.1002/jcp.70030","DOIUrl":"https://doi.org/10.1002/jcp.70030","url":null,"abstract":"<p>Caroline A. L., L. de Bortoli Teixeira, S. C. Simões, et al. 2021. <i>Journal of Cellular Physiology</i> 236, no. 6: 4640–4654.</p><p>In Figure 4B of “Results” section, the images representing GAPDH protein expression in the nucleus and Histone expression in the cytoplasm were inadvertently omitted. The correct images representative Western Blotting images are presented below.</p><p>The authors apologize for this error.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 4","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.70030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143818418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}