Cell Proliferation最新文献_第5页

Targeting FABP4 to Inhibit AGEs-RAGE/NF-κB Signalling Effectively Ameliorates Nucleus Pulposus Dysfunction and Angiogenesis in Obesity-Related Intervertebral Disc Degeneration. 靶向FABP4抑制age - rage /NF-κB信号传导可有效改善肥胖相关性椎间盘退变患者髓核功能障碍和血管生成

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2025-03-16 DOI: 10.1111/cpr.70021

Lin Han, Fudong Li, Huiqiao Wu, Weiheng Wang, Peiwen Chen, Weicheng Xia, Yang Liu, Kaiqiang Sun, Wenbo Lin

{"title":"Targeting FABP4 to Inhibit AGEs-RAGE/NF-κB Signalling Effectively Ameliorates Nucleus Pulposus Dysfunction and Angiogenesis in Obesity-Related Intervertebral Disc Degeneration.","authors":"Lin Han, Fudong Li, Huiqiao Wu, Weiheng Wang, Peiwen Chen, Weicheng Xia, Yang Liu, Kaiqiang Sun, Wenbo Lin","doi":"10.1111/cpr.70021","DOIUrl":"https://doi.org/10.1111/cpr.70021","url":null,"abstract":"Intervertebral disc degeneration (IVDD) is a primary contributor to low back pain, posing significant social and economic burdens. Increasing evidence shows that obesity contributes to IVDD, yet the underlying mechanisms remain elusive. Here, we firstly revealed a causal correlation between obesity and IVDD via a two-sample mendelian randomization analysis and identified fatty acid-binding protein 4 (FABP4) as the potential regulator to associate IVDD and obesity. Elevated FABP4 expression promoted extracellular matrix (ECM) disequilibrium and angiogenesis to exacerbate IVDD progression. Genetically knocking out or pharmacologically inhibiting FABP4 in high-fat diet-induced mice alleviated IVDD. Mechanistically, obesity activated the mammalian target of rapamycin complex 1 (mTORC1), which upregulated FABP4 expression, leading to the accumulation of advanced glycation end-products (AGEs) in intervertebral disc tissue. AGEs further activated the NF-κB signalling pathway, exacerbating ECM degradation and neovascularization. Conversely, rapamycin-mediated inhibition of mTORC1 suppressed FABP4 expression in nucleus pulposus cells (NPCs), alleviating IVDD in vivo. Collectively, our findings reveal a critical role of the obesity-induced mTORC1-FABP4 axis in ECM degradation and angiogenesis during IVDD progression. Targeting FABP4 may represent a promising therapeutic strategy for IVDD in obese individuals.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70021"},"PeriodicalIF":5.9,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tryptophan Metabolic Enzyme IL4I1 Inhibits Ferroptosis by Decreasing Ubiquitination of Nrf2 via I3P in Glioblastoma. 色氨酸代谢酶IL4I1通过I3P降低Nrf2泛素化抑制胶质母细胞瘤中的铁凋亡。

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2025-03-12 DOI: 10.1111/cpr.13816

Yang Xu, Yu Hong, Tengfeng Yan, Qian Sun, Fanen Yuan, Shanwen Liang, Liguo Ye, Rongxin Geng, Yangzhi Qi, Qingsong Ye, Qianxue Chen

{"title":"Tryptophan Metabolic Enzyme IL4I1 Inhibits Ferroptosis by Decreasing Ubiquitination of Nrf2 via I3P in Glioblastoma.","authors":"Yang Xu, Yu Hong, Tengfeng Yan, Qian Sun, Fanen Yuan, Shanwen Liang, Liguo Ye, Rongxin Geng, Yangzhi Qi, Qingsong Ye, Qianxue Chen","doi":"10.1111/cpr.13816","DOIUrl":"https://doi.org/10.1111/cpr.13816","url":null,"abstract":"Glioblastoma multiforme (GBM) is the deadliest brain tumour with an extremely poor prognosis. Tryptophan catabolism could enhance an array of protumour-genic signals and promoted tumour progression in GBM. However, the mechanisms of oncogenic signalling under tryptophan catabolism and potential therapy targeting this pathway have not been completely understood. Interleukin 4-induced 1 (IL4I1) is newly defined as a tryptophan metabolic enzyme and the potential function in GBM cells still remains unclear. In our study, we found IL4I1 was upregulated in GBM patients and predicted poor prognosis. Upregulation of IL4I1 inhibited GBM ferroptosis in vitro and in vivo. Further, we found that indole-3-pyruvic acid (I3P) from tryptophan mediated by IL4I1 could scavenge free radical and had an impressive role in inhibiting ferroptosis. To clarify the potential mechanism of I3P in GBM ferroptosis, we performed transcriptomic analyses of GBM cells treated with I3P and found that Nrf2 related genes was upregulated. Further, we found that the ubiquitination of Nrf2 could be attenuate by I3P binding with Nrf2 directly. Knockdown of Nrf2 attenuated the induction of anti-ferroptosis by IL4I1, pointing to Nrf2 as a key mediator of this process. In vivo, overexpression of IL4I1 with ML385 in GBM xenografts promoted ferroptosis. Collectively, this study emphasises the crucial roles of IL4I1 in anti-ferroptosis through Nrf2 signalling pathway but not AHR pathway by catabolism tryptophan, suggesting IL4I1 and tryptophan reprogramming as potential therapeutic targets for GBM.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e13816"},"PeriodicalIF":5.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sirt3 Rescues Porphyromonas gingivalis-Impaired Cementogenesis via SOD2 Deacetylation. Sirt3通过SOD2去乙酰化拯救牙龈卟啉单胞菌受损的骨质形成。

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2025-03-11 DOI: 10.1111/cpr.70022

Xin Huang, Huiqing Gou, Jirong Xie, Yonglin Guo, Yifei Deng, Yan Xu, Zhengguo Cao

{"title":"Sirt3 Rescues Porphyromonas gingivalis-Impaired Cementogenesis via SOD2 Deacetylation.","authors":"Xin Huang, Huiqing Gou, Jirong Xie, Yonglin Guo, Yifei Deng, Yan Xu, Zhengguo Cao","doi":"10.1111/cpr.70022","DOIUrl":"https://doi.org/10.1111/cpr.70022","url":null,"abstract":"The keystone pathogen Porphyromonas gingivalis (P.g.) is responsible for cementum resorption in periodontitis; however, the mechanism involved in it remains unclear. Sirtuin 3 (Sirt3) is a NAD+-dependent protein deacetylase contributing to mitochondrial homeostasis and various cell functions. In this study, the expression of Sirt3 in cementoblasts was found to be increased during cementoblast mineralisation and cementum development, while it decreased gradually under P.g. infection in a multiplicity of infection-dependent manner. Compared with wild type mice, the Sirt3 knockout mice showed less cellular cementum and lower mineralisation capacity with decreased expression of Runx2 and OCN in cementoblasts. Sirt3 inhibition by 3-TYP or Sirt3 silencing by lentivirus infection both confirmed the impaired cementogenesis. Conversely, honokiol (HKL) was simulated to bind Sirt3 and was applied to activate Sirt3 in cementoblasts. HKL-mediated Sirt3 activation facilitated cementoblast mineralisation and rescued P.g.-suppressed cementoblast mineralisation markedly. Superoxide dismutase 2 (SOD2), the downstream molecule of Sirt3, showed a similar expression pattern to Sirt3 under different conditions. Silencing of SOD2 was demonstrated to restrain cementoblast mineralisation. The pan acetylation was detected to decrease under Sirt3-upregulating conditions and increase under Sirt3-downregulating conditions. The binding of Sirt3 and SOD2 in cementoblasts was also verified. Furthermore, SOD2 acetylation and specific SOD2-K68 acetylation were found to be upregulated under P.g. or Sirt3 silencing conditions and downregulated by HKL stimulation. Moreover, K68Q mutation simulating acetylation decreased cementoblast mineralisation, while K68R mutation simulating deacetylation increased it. Altogether, Sirt3 deacetylates SOD2 via K68 to orchestrate P.g.-perturbed cementogenesis, and HKL is a Sirt3-targeted treatment candidate.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70022"},"PeriodicalIF":5.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rapid and Effective Neuronal Conversion of Human Glioblastoma In Vitro and In Vivo Using Potent Small Molecules. 利用有效的小分子在体外和体内快速有效地转化人胶质母细胞瘤的神经元。

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2025-03-11 DOI: 10.1111/cpr.70013

Ya'nan Hu, Jinming Liu, Jian Tu, Min Yang, Qisheng He, Fei Li, Xiaojing Xu, Zhongqing Ji, Jianwei Xu, Wentao Zhong, Mengwen Yan, Ying Yang, Huanxiang Zhang

{"title":"Rapid and Effective Neuronal Conversion of Human Glioblastoma In Vitro and In Vivo Using Potent Small Molecules.","authors":"Ya'nan Hu, Jinming Liu, Jian Tu, Min Yang, Qisheng He, Fei Li, Xiaojing Xu, Zhongqing Ji, Jianwei Xu, Wentao Zhong, Mengwen Yan, Ying Yang, Huanxiang Zhang","doi":"10.1111/cpr.70013","DOIUrl":"https://doi.org/10.1111/cpr.70013","url":null,"abstract":"Exploring effective, prompt and universally applicable approaches for inducing the differentiation of glioblastoma (GBM) into terminally differentiated cells, such as astrocytes or neurons that cease cell division, is pivotal for the success of GBM differentiation therapy. In this study, a neuronal-specific promoter-reporter system was employed to screen small molecules that promote neural differentiation. The cocktail YFSS, consisting of Y27632, Forskolin, SB431542 and SP600125, which selectively targets the ROCK, cAMP, TGF-β and JNK signalling pathways, respectively, was found to effectively trigger differentiation in human GBM cells. This process yielded neuron-like cells within 7 days, inhibited GBM cell proliferation and reduced malignancy traits, such as stemness, migratory and invasive capabilities. Transcriptome sequencing revealed the pathways altered by YFSS, shedding light on its dual role in halting cell proliferation and initiating neuronal differentiation. A notable increase in CEND1 expression, a key molecule in cell cycle and neuronal differentiation regulation, was observed during differentiation. However, CEND1 alone could not replicate YFSS's high conversion efficiency and its depletion reduced the differentiation and restored proliferation of the GBM cells. In vivo, prolonged and localised YFSS application significantly curtailed tumour growth and extended survival in patient-derived xenograft mice models. In summary, our findings reveal that the small-molecule cocktail YFSS is an effective means for inducing neuronal differentiation in GBM cells, representing a novel and promising pathway for the advancement of GBM treatment.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70013"},"PeriodicalIF":5.9,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting Regulation of Macrophage to Treat Metabolic Disease: Role of Phytochemicals. 巨噬细胞靶向调控治疗代谢性疾病：植物化学物质的作用。

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2025-03-05 DOI: 10.1111/cpr.70012

Zeting Ye, Yanlin Li, Xiaolin Yang, Chenglin Li, Rui Yu, Guangjuan Zheng, Zuqing Su

{"title":"Targeting Regulation of Macrophage to Treat Metabolic Disease: Role of Phytochemicals.","authors":"Zeting Ye, Yanlin Li, Xiaolin Yang, Chenglin Li, Rui Yu, Guangjuan Zheng, Zuqing Su","doi":"10.1111/cpr.70012","DOIUrl":"https://doi.org/10.1111/cpr.70012","url":null,"abstract":"Metabolic syndrome encompasses a cluster of predictive metabolic risk factors, including obesity, insulin resistance, dyslipidemia, hyperglycemia and hypertension. It is strongly associated with the development of type 2 diabetes and cardiovascular disease. Given the increasing morbidity and mortality associated with metabolic syndrome, along with the limited availability of drug treatments, it is high time to investigate the pathogenesis of this condition and explore potential pharmacotherapies. Macrophages, well-known innate immune cells, play an essential role in maintaining tissue immune homeostasis and multiple physiological processes, including glucose and lipid metabolism, oxidative stress and inflammation. Emerging evidence indicates that the effects of macrophages in metabolic syndrome are linked to macrophage-mediated metaflammation. Phytochemicals derived from natural plants have been shown to exert therapeutic effects on metabolic syndrome by modulating macrophage function. In this review, we sort out the role of macrophage-mediated metaflammation in the pathogenesis of metabolic syndrome and summarise potential phytochemicals that target macrophages for the treatment of this condition.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70012"},"PeriodicalIF":5.9,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Featured Cover 了封面

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2025-03-05 DOI: 10.1111/cpr.13822

Lanyang Gao, Lin Gao, Shiyao Huang, Lei Sun, Mei Li, Chen Shen, Youyou Chen, Ruihao Tan, Yuji Chen, Chengguo Zhan, Frank Heinrich Wieland, Yingying Liu, Yinan Zhang, Yao Luo

引用次数: 0

Multi-Omics Reveal the Metabolic Changes in Cumulus Cells During Aging. 多组学揭示衰老过程中积云细胞的代谢变化。

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2025-03-05 DOI: 10.1111/cpr.70014

Liangyue Shi, Hengjie Wang, Shuai Zhu, Minjian Chen, Xuejiang Guo, Qiang Wang, Ling Gu

{"title":"Multi-Omics Reveal the Metabolic Changes in Cumulus Cells During Aging.","authors":"Liangyue Shi, Hengjie Wang, Shuai Zhu, Minjian Chen, Xuejiang Guo, Qiang Wang, Ling Gu","doi":"10.1111/cpr.70014","DOIUrl":"https://doi.org/10.1111/cpr.70014","url":null,"abstract":"Maternal age has been reported to impair oocyte quality. However, the molecular mechanisms underlying the age-related decrease in oocyte competence remain poorly understood. Cumulus cells establish direct contact with the oocyte through gap junctions, facilitating the provision of crucial nutrients necessary for oocyte development. In this study, we obtained the proteomic and metabolomic profiles of cumulus cells from both young and old mice. We found that fatty acid beta-oxidation and nucleotide metabolism, markedly active in aged cumulus cells, may serve as a compensatory mechanism for energy provision. Tryptophan undergoes two principal metabolic pathways, including the serotonin (5-HT) synthesis and kynurenine catabolism. Notably, we discovered that kynurenine catabolism is reduced in aged cumulus cells compared to young cells, whereas 5-HT synthesis exhibited a significant decrease. Furthermore, the supplement of 5-HT during cumulus-oocyte complexes (COCs) culture significantly ameliorated the metabolic dysfunction and meiotic defects in old oocytes. In sum, our data provide a comprehensive multiple omics resource, offering potential insights for improving oocyte quality and promoting fertility in aged females.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70014"},"PeriodicalIF":5.9,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the Therapeutic Potential of MIR-140-3p in Osteoarthritis: Targeting CILP and Ferroptosis for Novel Treatment Strategies. 探索骨关节炎中 MIR-140-3p 的治疗潜力：以 CILP 和铁肽化为靶点的新型治疗策略。

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2025-03-05 DOI: 10.1111/cpr.70018

Feng Ma, Lexin Wang, Hao Chi, Xinyi Li, Yaoqin Xu, Kexin Chen, Jingfan Zhou, Runqin Yang, Jie Liu, Ke Xu, Xiaoling Yang

{"title":"Exploring the Therapeutic Potential of MIR-140-3p in Osteoarthritis: Targeting CILP and Ferroptosis for Novel Treatment Strategies.","authors":"Feng Ma, Lexin Wang, Hao Chi, Xinyi Li, Yaoqin Xu, Kexin Chen, Jingfan Zhou, Runqin Yang, Jie Liu, Ke Xu, Xiaoling Yang","doi":"10.1111/cpr.70018","DOIUrl":"https://doi.org/10.1111/cpr.70018","url":null,"abstract":"Osteoarthritis (OA) is a prevalent and debilitating joint disorder that affects millions of individuals worldwide, severely impairing mobility, independence, and quality of life. Emerging evidence suggests that ferroptosis is a critical factor in OA pathogenesis. However, its precise involvement and underlying mechanisms remain poorly understood. In this study, we first identified that cartilage intermediate layer protein (CILP) mediates the regulation of ferroptosis-related genes in OA through hdWGCNA analysis combined with single-cell RNA sequencing. Further investigation revealed a significant upregulation of CILP protein expression in C28/I2 cells under LPS induction. Mechanistically, bioinformatics analysis identified differentially expressed miRNAs; qRT-PCR combined with a dual-luciferase experiment revealed that miR-140-3p was downregulated and directly targets CILP. Experimental data further demonstrated that miR-140-3p regulates ferroptosis, inflammation, and oxidative stress by targeting CILP. These findings offer valuable insights into the molecular mechanisms of the miR-140-3p/CILP axis in regulating ferroptosis, inflammation, and oxidative stress, thus providing a foundation for developing therapeutic strategies for OA.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70018"},"PeriodicalIF":5.9,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Elevated COMMD1 Contributes to Cardiomyocyte Copper Efflux in Chronic Myocardial Ischemia: Insights From Rhesus Monkey. 慢性心肌缺血时COMMD1升高与心肌细胞铜外排有关：来自恒河猴的见解。

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2025-03-03 DOI: 10.1111/cpr.70016

Chen Li, Da Li, Xia Cheng, Xiaoli Yuan, Ning Du, Xin Liao, Xiaorong Feng, Jie Yao, Chenglong Li, Chengxia Xie, Mu Yang

{"title":"Elevated COMMD1 Contributes to Cardiomyocyte Copper Efflux in Chronic Myocardial Ischemia: Insights From Rhesus Monkey.","authors":"Chen Li, Da Li, Xia Cheng, Xiaoli Yuan, Ning Du, Xin Liao, Xiaorong Feng, Jie Yao, Chenglong Li, Chengxia Xie, Mu Yang","doi":"10.1111/cpr.70016","DOIUrl":"https://doi.org/10.1111/cpr.70016","url":null,"abstract":"Copper deficiency, commonly observed in myocardial infarction, leads to cardiomyocyte loss and cardiac dysfunction, yet the mechanism driving copper efflux remains unclear. To further elucidate the relationship between copper transporters and cardiac copper efflux during chronic myocardial ischemia, a rhesus monkey model was established by performing the permanent ligation of the left anterior descending coronary artery. A dramatic decrease in copper concentration within ischemic cardiomyocytes was observed alongside declining cardiac function. Among major copper transporters, COMMD1 and ATP7B were significantly upregulated in the ischemic myocardium. COMMD1 was specifically localised in cardiomyocytes undergoing copper efflux, whereas increased ATP7B was restricted to cardiac fibroblasts. This indicates that elevated COMMD1 regulates copper efflux in cardiomyocytes during chronic myocardial ischemia, functioning independently of its interactions with P-type ATPase transporters. Given the discrepancy between RNA and protein levels of COMMD1 in ischemic myocardium, post-translational modification is likely responsible for regulating COMMD1 expression. We found that the copper-binding protein with E3 ubiquitin ligase activity, XIAP, augmented before the rise in COMMD1 expression within ischemic cardiomyocytes. Excessive XIAP specifically interacted with COMMD1 to enhance its protein levels under copper-deprivation conditions and vice versa. Overall, our findings reveal a positive feedback loop among XIAP, COMMD1 and copper, highlighting the intricate interplay between XIAP and COMMD1 in regulating copper efflux in cardiomyocytes. This loop sets the stage for further investigation into therapeutic strategies to manage copper homeostasis in chronic myocardial ischemia.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70016"},"PeriodicalIF":5.9,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ezh2 Regulates Early Astrocyte Morphogenesis and Influences the Coverage of Astrocytic Endfeet on the Vasculature. Ezh2调控早期星形细胞形态发生，影响星形细胞终足对血管的覆盖。

IF 5.9 1区生物学

Cell Proliferation Pub Date : 2025-02-28 DOI: 10.1111/cpr.70015

Xinghua Zhao, Mengtian Zhang, WenZheng Zou, Chenxiao Li, Shukui Zhang, Yuqing Lv, Libo Su, Fen Ji, Jianwei Jiao, Yufei Gao

{"title":"Ezh2 Regulates Early Astrocyte Morphogenesis and Influences the Coverage of Astrocytic Endfeet on the Vasculature.","authors":"Xinghua Zhao, Mengtian Zhang, WenZheng Zou, Chenxiao Li, Shukui Zhang, Yuqing Lv, Libo Su, Fen Ji, Jianwei Jiao, Yufei Gao","doi":"10.1111/cpr.70015","DOIUrl":"https://doi.org/10.1111/cpr.70015","url":null,"abstract":"Astrocytes are crucial for central nervous system (CNS) development and function, with their differentiation being stringently controlled by epigenetic mechanisms, such as histone modifications. Enhancer of Zeste Homologue 2 (EZH2), a histone methyltransferase, is essential for the suppression of gene expression. However, the role of EZH2 in astrocyte early morphogenesis has remained unclear. Using an astrocyte-specific Ezh2 knockout (cKO) mouse model, we examined the effects of EZH2 deletion on astrocyte morphogenesis, blood-brain barrier (BBB) integrity and neurodevelopment. Loss of EZH2 led to increased glial fibrillary acidic protein (GFAP) expression, altered astrocyte morphology and reduced coverage of astrocytic endfeet on blood vessels, compromising BBB integrity. Vascular abnormalities, characterised by increased vascular density and smaller vessel diameter, mirrored compensatory changes seen in moyamoya disease. RNA-sequencing and ChIP-seq identified Ddn as a key upregulated gene in Ezh2cKO astrocytes, influencing cytoskeletal changes via the MAPK/ERK pathway. Behavioural analysis revealed autism-like traits, such as reduced vocalisations, without significant anxiety-like behaviour. These findings highlight EZH2 as a critical regulator of astrocyte function, with its disruption contributing to neurodevelopmental disorders. This study provides novel insights into the molecular pathways governing astrocyte differentiation and suggests EZH2 as a promising therapeutic target for gliomas and other CNS disorders.","PeriodicalId":9760,"journal":{"name":"Cell Proliferation","volume":" ","pages":"e70015"},"PeriodicalIF":5.9,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0