Journal of Cellular Physiology最新文献

{"title":"CBFβ Regulates RUNX3 ADP-Ribosylation to Mediate Homologous Recombination Repair","authors":"William E. Samsa,&nbsp;Zhen Zhang,&nbsp;Zihua Gong","doi":"10.1002/jcp.31503","DOIUrl":"10.1002/jcp.31503","url":null,"abstract":"<div>\u0000 \u0000 <p>RUNX3 is a master developmental transcriptional factor that has been implicated as a tumor suppressor in many cancers. However, the exact role of RUNX3 in cancer pathogenesis remains to be completely elucidated. Recently, it has emerged that RUNX3 is involved in the DNA damage response. Here, we demonstrate that heterodimerization of RUNX3 with CBFβ is necessary for its stability by protecting RUNX3 from RUNX3 ADP-ribosylation-dependent ubiquitination and degradation. We further identify new amino acid residues that are targets for PARylation and demonstrate that RUNX3 PARylation at these residues is necessary for localization of RUNX3 to DNA double strand break sites (DBSs). We also demonstrate that both RUNX3 PARylation and CBFβ heterodimerization with RUNX3 positively regulates homologous recombination (HR) repair, in part by promoting the recruitment of CtIP and phospho-RPA2 to the DBSs to mediate HR repair. In summary, we provide evidence that RUNX3 regulates HR repair activity in a PARylation-dependent manner.</p>\u0000 </div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854241","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":"Novel Therapeutic Strategies Targeting Fibroblasts to Improve Heart Disease","authors":"Yujuan Li","doi":"10.1002/jcp.31504","DOIUrl":"10.1002/jcp.31504","url":null,"abstract":"<div>\u0000 \u0000 <p>Cardiac fibrosis represents the terminal pathological manifestation of various heart diseases, with the formation of fibroblasts playing a pivotal role in this process. Consequently, targeting the formation and function of fibroblasts holds significant potential for improving outcomes in heart disease. Recent research reveals the considerable potential of fibroblasts in ameliorating cardiac conditions, demonstrating different functional characteristics at various time points and spatial locations. Therefore, precise modulation of fibroblast activity may offer an effective approach for treating cardiac fibrosis and achieving targeted therapeutic outcomes. In this review, we focus on the fate and inhibition of fibroblasts, analyze their dynamic changes in cardiac diseases, and propose a framework for identifying markers of fibroblast activation mechanisms and selecting optimal time windows for therapeutic intervention. By synthesizing research findings in these areas, we aim to provide new strategies and directions for the precise treatment of fibroblasts in cardiac diseases.</p>\u0000 </div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846675","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":"RRM2 Is a Putative Biomarker and Promotes Bladder Cancer Progression via PI3K/AKT/mTOR Pathway","authors":"Linfa Guo,&nbsp;Yiqiao Zhao,&nbsp;Xiaojie Bai,&nbsp;Xiaolong Wang,&nbsp;Kuerban Tuoheti,&nbsp;Yuanfei Cao,&nbsp;Yingtong Zuo,&nbsp;Xinhua Zhang,&nbsp;Tongzu Liu","doi":"10.1002/jcp.31501","DOIUrl":"10.1002/jcp.31501","url":null,"abstract":"<div>\u0000 \u0000 <p>Bladder cancer (BLCA) is the tenth most common cancer worldwide, characterized by its high recurrence and progression rates. Thus, identifying prognostic biomarkers and understanding its underlying mechanisms are imperative to enhance patient outcomes. In this study, we aimed to investigate the prognostic significance, expression, functional activity, and underlying mechanisms of RRM2 in BLCA. RRM2 expression and its association with pathological grading and survival were investigated in samples from TCGA dataset and BLCA tissue microarray. CCK8 assays, colony formation assays, wound healing, and transwell assays were performed to assess the role of RRM2 in BLCA cell proliferation and migration. Western blot was employed to investigate alterations in markers associated with epithelial-to-mesenchymal transition (EMT), apoptosis, and cell cycle regulation. Gene set enrichment analysis was performed to investigate the biological processes associated with RRM2, which were subsequently validated. The expression of RRM2 was significantly elevated in both BLCA tissues and cells. Our results also indicated a positive correlation between RRM2 expression and high tumor stage, high tumor grade, and poor survival. Knockdown of RRM2 inhibited cell proliferation and migration of BLCA. RRM2 knockdown significantly induced apoptosis and arrested the cell cycle at the G0/G1 phase. Opposite results were observed in the RRM2 overexpression cells. Additionally, our study demonstrates that RRM2 promotes BLCA progression by activating the PI3K/AKT/mTOR pathway. RRM2 is remarkably correlated with poor prognosis in BLCA and facilitate its progression via PI3K/AKT/mTOR pathway. It is suggested that RRM2 might become an effective prognostic biomarker and potential therapeutic target for BLCA.</p></div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828602","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":"Cover Image, Volume 239, Number 12, December 2024","authors":"Yongya Zhang,&nbsp;Fei Wu,&nbsp;Sibei Guo,&nbsp;Ruijie Yin,&nbsp;Min Yuan,&nbsp;Xue Li,&nbsp;Xueru Zhao,&nbsp;Xiaohua Li","doi":"10.1002/jcp.31514","DOIUrl":"https://doi.org/10.1002/jcp.31514","url":null,"abstract":"<p><b>Inside Front Cover Caption:</b> The cover image is based on the article <i>Critical role of apoptosis in MeCP2-mediated epithelial–mesenchymal transition of ARPE-19 cells</i> by Xiaohua Li et al., https://doi.org/10.1002/jcp.31429.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"239 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.31514","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142861500","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":"Pregnancy Entails a Metabolic Rewiring of Maternal Circulating Neutrophils","authors":"Guillermina Calo,&nbsp;Fátima Merech,&nbsp;Florencia Sabbione,&nbsp;Vanesa Hauk,&nbsp;Brenda Lara,&nbsp;Luciana Doga,&nbsp;Luciana D'eramo,&nbsp;Aldo Squassi,&nbsp;Rosanna Ramhorst,&nbsp;Analía Trevani,&nbsp;Daiana Vota,&nbsp;Claudia Pérez Leirós","doi":"10.1002/jcp.31502","DOIUrl":"10.1002/jcp.31502","url":null,"abstract":"<div>\u0000 \u0000 <p>Immunometabolism is an emerging growing field that focuses on the role of cellular metabolism in the regulation of immune cell function and fate. Thus, proliferation, differentiation, activation, and function of immune cell populations are modulated by reprogramming their fueling and metabolic pathways. Pregnancy entails a fine immune and metabolic regulation of the maternal−fetal interaction to assist the energetic demands of the fetus where trophoblast cells have a central role. Maternal neutrophil functional shaping by trophoblast cells has been proposed though their metabolic conditioning during pregnancy has not been studied yet. Here, we explored the effects of trophoblast-derived factors on the metabolic rewiring of neutrophils from nonpregnant women and its impact on central functions like reactive oxygen species (ROS) production, neutrophil extracellular trap (NET) release, and migration. In parallel, the immunometabolic status and function of neutrophils isolated from pregnant women (16−20 weeks) was compared with nonpregnant age-matched control samples. Trophoblast-derived factors induced glucose uptake and lipid droplet accumulation without activating ROS production or NET release. Conditioned media from trophoblast cells also inhibited PMA-induced NETosis partly by impairing glucose uptake in neutrophils. In turn, neutrophils from pregnant women had increased basal ROS production, lipid accumulation, and glucose uptake compared to neutrophils from nonpregnant women, accompanied by a higher release of PMA-induced NETs. Interestingly, PMA-induced NETs was blocked by a fatty acid oxidation inhibitor in neutrophils from pregnant women indicating the contribution of fatty acid metabolism to neutrophil activity during pregnancy. Results are consistent with immunometabolic mechanisms underlying the functional shaping of neutrophils during pregnancy and point out the contribution of trophoblast-derived factors to their metabolic profiling. These findings provide novel immunometabolic clues to understand immune homeostasis maintenance during pregnancy and raise the clinical potential of monitoring neutrophil metabolism during normal and complicated pregnancies.</p>\u0000 </div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828657","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":"Cover Image, Volume 239, Number 12, December 2024","authors":"Irene Bottillo,&nbsp;Andrea D'Alessandro,&nbsp;Maria Pia Ciccone,&nbsp;Gianluca Cestra,&nbsp;Gianluca Di Giacomo,&nbsp;Evelina Silvestri,&nbsp;Marco Castori,&nbsp;Francesco Brancati,&nbsp;Andrea Lenzi,&nbsp;Alessandro Paiardini,&nbsp;Silvia Majore,&nbsp;Giovanni Cenci,&nbsp;Paola Grammatico","doi":"10.1002/jcp.31513","DOIUrl":"https://doi.org/10.1002/jcp.31513","url":null,"abstract":"<p><b>Front Cover Caption:</b> The cover image is based on the article <i>An inherited TBX3 alteration in a prenatal case of ulnar-mammary syndrome: Clinical assessment and functional characterization in Drosophila melanogaster</i> by Giovanni Cenci et al., https://doi.org/10.1002/jcp.31440.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"239 12","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.31513","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142861499","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":"Exploring Metabolic Approaches for Epithelial Ovarian Cancer Therapy","authors":"Sangeeta Kumari,&nbsp;Shraddha Gupta,&nbsp;Aisha Jamil,&nbsp;Deyana Tabatabaei,&nbsp;Sergey Karakashev","doi":"10.1002/jcp.31495","DOIUrl":"10.1002/jcp.31495","url":null,"abstract":"<div>\u0000 \u0000 <p>Epithelial ovarian cancer (EOC) has the highest mortality rate among malignant tumors of the female reproductive system and the lowest survival rate. This poor prognosis is due to the aggressive nature of EOC, its late-stage diagnosis, and the tumor's ability to adapt to stressors through metabolic reprogramming. EOC cells sustain their rapid proliferation by altering the uptake, utilization, and regulation of carbohydrates, lipids, and amino acids. These metabolic changes support tumor growth and contribute to metastasis, chemotherapy resistance, and immune evasion. Targeting these metabolic vulnerabilities has shown promise in preclinical studies, with some therapies advancing to clinical trials. However, challenges remain due to tumor heterogeneity, adaptive resistance mechanisms, and the influence of the tumor microenvironment. This review provides a comprehensive summary of metabolic targets for EOC treatment and offers an overview of the current landscape of clinical trials focusing on ovarian cancer metabolism. Future efforts should prioritize combination therapies that integrate metabolic inhibitors with immunotherapies or chemotherapy. Advances in precision medicine and multi-omics approaches will be crucial for identifying patient-specific metabolic dependencies and improving outcomes. By addressing these challenges, metabolism-based therapies can significantly transform the treatment of this devastating disease.</p>\u0000 </div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828655","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":"Muscle PGC-1α Overexpression Drives Metabolite Secretion Boosting Subcutaneous Adipocyte Browning","authors":"Caterina Miro,&nbsp;Ciro Menale,&nbsp;Lucia Acampora,&nbsp;Annarita Nappi,&nbsp;Serena Sagliocchi,&nbsp;Federica Restolfer,&nbsp;Sepehr Torabinejad,&nbsp;Mariano Stornaiuolo,&nbsp;Monica Dentice,&nbsp;Annunziata Gaetana Cicatiello","doi":"10.1002/jcp.31480","DOIUrl":"10.1002/jcp.31480","url":null,"abstract":"<p>Muscle and adipose tissue (AT) are in mutual interaction through the integration of endocrine and biochemical signals, thus regulating whole-body function and physiology. Besides a traditional view of endocrine relationships that imply the release of cytokines and growth factors, it is becoming increasingly clear that a metabolic network involving metabolites as signal molecules also exists between the two tissues. By elevating the number and functionality of mitochondria, a key role in muscle metabolism is played by the master regulator of mitochondrial biogenesis peroxisome-proliferator-activated receptor-γ coactivator-1α (PGC-1α), that induces a fiber type shift from glycolytic to oxidative myofibers. As a consequence, the upregulation of muscle respiratory rate might affect metabolite production and consumption. However, the underlying mechanisms have not yet been fully elucidated. Here, we used a muscle-specific PGC-1α overexpressing mouse model (MCK-PGC-1α) to analyze the metabolite secretion profile of serum and culture medium recovered from MCK-PGC-1α muscle fibers by NMR. We revealed modified levels of different metabolites that might be ascribed to the metabolic activation of the skeletal muscle fibers. Notably, the dysregulated levels of these metabolites affected adipocyte differentiation, as well as the browning process in vitro and in vivo. Interestingly such effect was exacerbated in the subcutaneous WAT, while only barely present in the visceral WAT. Our data confirm a prominent role of PGC-1α as a trigger of mitochondrial function in skeletal muscle and propose a novel function of this master regulator gene in modulating the metabolite production in turn affecting the activation of WAT and its conversion toward the browning.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828656","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":"Regulation of the Cilia as a Potential Treatment for Senescence and Tumors: A Review","authors":"Danping Zhu,&nbsp;Yuqin Pan,&nbsp;Yong Yang,&nbsp;Shukui Wang","doi":"10.1002/jcp.31499","DOIUrl":"10.1002/jcp.31499","url":null,"abstract":"<div>\u0000 \u0000 <p>Millions of people worldwide die from malignant tumors every year, and the current clinical treatment is still based on radiotherapy and chemotherapy. Immunotherapy-adjuvant chemotherapy is widely applied, yet resistance to various factors persists in the management of advanced malignancies. Recently researchers have gradually discovered that the integrity of primary cilia is closely related to many diseases. The phenotypic changes in primary cilia are found in some cases of progeria, tumorigenesis, and drug resistance. Primary cilia seem to mediate signaling during these diseases. Hedgehog inhibitors have emerged in recent years to treat tumors by controlling signaling proteins on primary cilia. There is evidence for the use of anti-tumor drugs to treat senescence-related disease. Considering the close relationship between aging and obesity, as well as the obesity is the phenotype of many ciliopathies. Therefore, we speculate that some anti-tumor or anti-aging drugs can treat ciliopathies. Additionally, there is evidence suggesting that anti-aging drugs for tumor treatment, in which the process may be mediated by cilia. This review elucidates for the first time that cilia may be involved in the regulation of senescence, metabolic, tumorigenesis, and tumor resistance and hypothesizes that cilia can be regulated to treat these diseases in the future.</p>\u0000 </div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806804","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":"DMT1 Maintains Iron Homeostasis to Regulate Mitochondrial Function in Porcine Oocytes","authors":"Jin-Xin Zhang,&nbsp;Meng-Fan Lan,&nbsp;Jian-Zhou Shang,&nbsp;Xin-Le Lai,&nbsp;Li-Shu Li,&nbsp;Tong-Tong Duan,&nbsp;Ru-Hai Xu,&nbsp;Kun-Lin Chen,&nbsp;Xing Duan","doi":"10.1002/jcp.31494","DOIUrl":"10.1002/jcp.31494","url":null,"abstract":"<div>\u0000 \u0000 <p>Iron plays critical roles in many cellular functions, including energy production, metabolism, and cell proliferation. However, the role of iron in maintaining oocyte quality remains unclear. In this study, DMT1 was identified as a key iron transporter during porcine oocyte maturation. The results demonstrated that iron deficiency in porcine oocyte led to aberrant meiotic progression, accompanied by increased gene expression of <i>DMT1</i>. Inhibition of DMT1 resulted in the failure of cumulus cell expansion and oocyte maturation, along by the abnormal actin and microtubule assembly. Furthermore, loss of DMT1 function caused disruption in mitochondrial function and dynamics, resulting in oxidative stress and Ca²⁺ dyshomeostasis. Additionally, the absence of DMT1 function activated PINK1/Parkin-dependent mitophagy in porcine oocyte. These findings suggested that DMT1 played a crucial role in safeguarding oocyte quality by protecting against iron-deficiency-induced mitochondrial dysfunction and autophagy. This study provided compelling evidence that DMT1 and iron homeostasis were crucial for maintaining the capacity of porcine oocyte maturation. Moreover, the results hinted at the potential of DMT1 as a novel therapeutic target for treating iron deficiency-related female reproductive disorders.</p></div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 1","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785416","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}