Cell and Bioscience最新文献

{"title":"FAK-dependent activation of src family kinase member BLK contributed to endometrial fibrosis via endoplasmic reticulum stress.","authors":"Yimeng Lu, Xudong Zhang, Shanshan Wu, Siwen Zhang, Xiaohan Qi, Jichun Tan","doi":"10.1186/s13578-025-01492-w","DOIUrl":"10.1186/s13578-025-01492-w","url":null,"abstract":"<p><strong>Background: </strong>While Src family kinases (SFKs) are established mediators of some fibrotic diseases, their specific function in endometrial fibrosis is not well defined. Here, we investigated the function and underlying mechanism of B lymphoid tyrosine kinase (BLK), an SFK member, in driving endometrial fibrosis.</p><p><strong>Methods: </strong>BLK expression was analyzed in the human endometrium and mice uterus, as well as in human endometrial stromal cells (hEndoSCs). Its functional role was assessed using siBLK in TGF-β1-induced hEndoSCs and in the intrauterine adhesion (IUA) mice model with Blk knockdown (IUA^Blk[LKD]).</p><p><strong>Results: </strong>BLK was overexpressed and activated in the endometrium of IUA patients, the uterus of IUA mice, and TGF-β1-induced hEndoSCs, and was accompanied by high expression of endoplasmic reticulum stress (ERS) hallmarks GRP78 and CHOP. Inhibition of BLK significantly reduced the expression levels of GRP78, CHOP, Collagen I, and α-SMA in TGF-β1-induced hEndoSCs. Endometrial fibrosis was also significantly attenuated in IUA^Blk[LKD] mice. Phospho-activation of BLK was found to rely on its binding with focal adhesion kinase (FAK) to form a complex, and subsequently aggravated endometrial fibrosis by regulating ERS.</p><p><strong>Conclusions: </strong>Our findings clarified the critical role and possible mechanism of BLK in endometrial fibrosis. BLK may serve as a promising target for treating endometrial fibrosis.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"150"},"PeriodicalIF":6.2,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12577442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145423168","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":"Sexual dimorphism in colon is mediated by an androgen-IL33⁺ stromal cell axis.","authors":"Haoyu Wang, Baowei Jing, Juan Zou, Tian Lan, Mengxin Hu, Lan Lin, Hanhua Cheng, Rongjia Zhou","doi":"10.1186/s13578-025-01493-9","DOIUrl":"10.1186/s13578-025-01493-9","url":null,"abstract":"<p><strong>Background: </strong>Males and females exhibit pronounced disparity in the epidemiology, clinical progression, and therapeutic outcomes of colonic diseases, but the underlying mechanisms that regulate sexual dimorphism of colon remain poorly understood.</p><p><strong>Results: </strong>We determined the colon as a pivotal androgen metabolic hub, where gonad-derived androgens drive sex-dimorphic levels, while androgen-metabolizing enzymes maintain androgen homeostasis in colon. We identified IL-33⁺ colonic stromal cells as the dominant AR-expressing population in colon. Mechanistically, sex-biased androgen levels govern the nuclear translocation of androgen receptor and further assembly of AR liquid-liquid phase-separated condensates in the immunomodulatory stromal cells of male colon. Notably, we uncovered AR-directed transcriptional programs via nuclear AR phase separation underlying sex-biased expression of key factors, including SerpinA3N and MT1, thereby defining molecular base for sex disparities through gonad-colon axis.</p><p><strong>Conclusion: </strong>These findings provide molecular and cellular base for sex disparities through an androgen-IL33⁺ stromal cell axis in colon.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"148"},"PeriodicalIF":6.2,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12574091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145402453","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":"BAP18, as a corepressor of AR together with the SIN3A/HDAC complex, promotes AR-positive triple-negative breast cancer progression.","authors":"Yiqi Zhang, Zining Jin, Yi Wu, Xueying Tang, Chunyu Wang, Shengli Wang, Yinlin Li, Tian Zhang, Feng Jin, Heng Lu, Yue Zhao, Ang Zheng","doi":"10.1186/s13578-025-01489-5","DOIUrl":"10.1186/s13578-025-01489-5","url":null,"abstract":"<p><strong>Background: </strong>Triple-negative breast cancer (TNBC) is considered a highly heterogeneous disease. Androgen receptor (AR)-positive TNBC is a subtype with distinct molecular features. However, the molecular mechanism underlying the modulation of the AR signaling pathway in TNBC is still elusive.</p><p><strong>Results: </strong>BPTF-associated protein of 18 kDa (BAP18) was significantly upregulated in AR-positive TNBC samples and was positively correlated with advanced disease stage and poor prognosis. BAP18 was shown to act as a transcriptional corepressor of AR in AR-positive TNBC cells and is involved in the promotion of AR-positive TNBC. Mechanically, BAP18 associates with AR and the SIN3A/HDAC subcomplex. BAP18 facilitates the recruitment of SIN3A/HDAC to androgen response elements (AREs) in the promoter regions of P21 and PTEN, subsequently leading to a reduced level of histone H4 acetylation on AREs.</p><p><strong>Conclusion: </strong>Our study revealed that BAP18, which acts as a novel AR corepressor, is involved in AR-positive TNBC progression, suggesting that BAP18 could be a potential therapeutic target for AR-positive TNBC patients.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"147"},"PeriodicalIF":6.2,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12574159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145402401","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":"IgD in nucleus of pro-B cells promotes pro-B cells proliferation by regulating E2F3 expression.","authors":"Yixiao Zhang, Yanqi Hou, Meng Yu, Xin Zhang, Shenghua Zhang, Zhu Zhu, Weiyan Xu, Jing Huang, Xiaoyan Qiu","doi":"10.1186/s13578-025-01490-y","DOIUrl":"10.1186/s13578-025-01490-y","url":null,"abstract":"<p><strong>Background: </strong>Immunoglobulin D (IgD) has historically been considered as a surface marker of mature B cell with its specific function being undefined. Until now, no evidence had been presented to suggest that IgD is also expressed in pro-B cells. This study was designed to elucidate the significance for IgD in early B cell development.</p><p><strong>Results: </strong>Here we developed a mouse model with a targeted deletion of IgD, and assessed the production of the IgM, IgG and IgA, as well as the generation of the antigen specific antibodies. The findings indicated no significant differences in these Ig levels between wild-type and IgD-deficient mice. However, we observed a notable reduction in the number of mature B cells, which led us to the surprising discovery that this decrease in B cell count begins at the pro-B cell stage. More significantly, we identified that IgD, in its intact tetrameric structure, is expressed in the nucleus of pro-B cells. Functionally, IgD appears to promote the proliferation of pro-B cells. Mechanistically, IgD exhibits a transcription factor-like activity, and directly binds to the promoter region of E2f3, a pro-proliferative transcription factor to drive the expression of E2f3, thereby promoting pro-B cells proliferation.</p><p><strong>Conclusions: </strong>Taken together, this novel insight into the physiological significance of IgD in B cell development has important implications for our understanding of immune system function.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"149"},"PeriodicalIF":6.2,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12573911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145402369","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":"Breaking the link between morphology and potency for mESCs.","authors":"Yixin Fan, Xiaomin Wang, Ziwei Zhai, Tao Huang, Wei Li, Zechuan Liang, Zhaoyi Ma, Yu Fu, Pengli Li, Junqi Kuang, Duanqing Pei","doi":"10.1186/s13578-025-01497-5","DOIUrl":"10.1186/s13578-025-01497-5","url":null,"abstract":"<p><strong>Background: </strong>In stem cell biology, a long-held structure-function relationship is the domed colony morphology and naïve pluripotency for mouse or human pluripotent stem cells. This link has provided a convenient way to recognize bona fide naïve pluripotent cells during derivation, passaging and characterization. However, the molecular basis of this link remains poorly understood.</p><p><strong>Results: </strong>We show that a loss of domed morphology may not impact the overall genetic architecture of naïve pluripotency in mouse embryonic stem cells (mESCs). We first generated stable mESC lines by knocking out Myh9 that encodes non-muscle myosin heavy chain IIA, resulting in colonies deprived of the typical domed morphology, but competent to differentiate into the three germ layers and chimeric mice. Modulating cell morphologies with inhibitors against kinases known to regulate myosin pathway also phenocopy the knockout in wild type mESCs.</p><p><strong>Conclusions: </strong>These results provide evidence that the domed morphology and potency can be uncoupled and suggest that domed structure is not a pre-requisite for acquiring and maintaining naïve pluripotency.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"146"},"PeriodicalIF":6.2,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12551208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145356499","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":"Ssrp governs germline development independent of the FACT complex in Drosophila spermatogenesis.","authors":"Xiaoning Tan, Yuhan Lou, Zhiyong Yin, Jiaqi Zhao, Jia Wang, Jichen Jin, Yunbo Wang, Yongmei Xi, Xiaohang Yang, Huimei Zheng","doi":"10.1186/s13578-025-01478-8","DOIUrl":"10.1186/s13578-025-01478-8","url":null,"abstract":"<p><strong>Background: </strong>The heterodimeric FACT complex (SSRP1/Ssrp and SUPT16H/Dre4) is primarily recognized as a chromatin remodeler. While mutations in this complex are linked to human intellectual disability and it maintains neural stem cell fate in flies, single-cell RNA sequencing reveals robust FACT complex expression in human testicular germ cells. Nevertheless, its specific functions during spermatogenesis remain unexplored.</p><p><strong>Methods: </strong>This study utilized Drosophila melanogaster as a model to investigate the roles of FACT complex during spermatogenesis. Germline-specific and somatic-specific knockdowns of Ssrp and dre4 combined with immunostaining were performed to assess their functions. Bulk and single-cell RNA sequencing analyses were conducted on Ssrp-deficient testes to investigate transcriptomic changes.</p><p><strong>Results: </strong>Our study uncovers context-dependent functions for Ssrp. In testis somatic cells, Ssrp collaborates with Dre4 to sustain cyst stem cell populations via estrogen-related receptor-mediated glycolytic activation. Remarkably, germline Ssrp operates independently of Dre4, governing transit-amplifying divisions and meiotic progression. Germline-specific Ssrp depletion, but not dre4 knockdown, induces male sterility, characterized by spermatogonial accumulation, mitotic asynchrony, and meiotic arrest within primary spermatocytes. Bulk and single-cell RNA sequencing analyses of Ssrp-deficient testes reveal systemic transcriptomic dysregulation, including suppression of metabolic programs (glycolysis and oxidative phosphorylation) and activation of MAPK/EGFR signaling. Ssrp loss disrupts sister centromere cohesion during meiosis I, as well as diminished ATP levels and aberrant CENP-A accumulation, suggesting a dual regulatory nexus linking energy metabolism to chromosomal stability.</p><p><strong>Conclusions: </strong>This work reveals previously unknown, context-dependent functions of Ssrp during Drosophila spermatogenesis. Ssrp emerges as a multifunctional orchestrator essential for both somatic and germline compartments of germline development. These findings provide crucial foundational insights into reproductive disorders associated with Ssrp dysfunction and underscore the importance of the FACT complex in male germ cell development.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"145"},"PeriodicalIF":6.2,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12542197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145349531","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":"LARP1 acts as a key mediator in preventing angiotensin II-induced cardiac dysfunction and fibrosis.","authors":"Haikuo Zheng, Chuang Yang","doi":"10.1186/s13578-025-01481-z","DOIUrl":"10.1186/s13578-025-01481-z","url":null,"abstract":"<p><strong>Background: </strong>Cardiac remodeling underlies many cardiovascular diseases and is characterized by cardiomyocyte hypertrophy, apoptosis, and interstitial fibrosis, leading to structural and functional deterioration of the heart. Angiotensin II (Ang II), a component of the renin-angiotensin system, drives pathological remodeling through hypertrophy and fibrosis. La-related protein 1 (LARP1), an RNA-binding protein involved in post-transcriptional regulation, has been implicated in cancer biology but its role in cardiovascular disease is largely unexplored. This study investigates the role of LARP1 in regulating Ang II-induced cardiac remodeling and its interaction with ATP2A2, a gene essential for calcium homeostasis.</p><p><strong>Methods: </strong>Human cardiac tissues from hypertrophic cardiomyopathy patients and healthy controls were analyzed for LARP1 mRNA and protein expression. A murine model of Ang II-induced cardiac hypertrophy was established, and LARP1 expression was modulated using adeno-associated virus serotype 9 (AAV9)-LARP1 and gene-deficient mice. Primary cardiomyocytes and cardiac fibroblasts were treated with Ang II to study LARP1 function in vitro. RNA immunoprecipitation, RNA pull-down, and actinomycin D assays were performed to investigate the interaction between ATP2A2 mRNA and LARP1 protein. Cardiac function, hypertrophy, and fibrosis were evaluated through echocardiography, histological staining, and molecular analyses.</p><p><strong>Results: </strong>LARP1 mRNA and protein expression were significantly downregulated in hypertrophic human and murine cardiac tissues and in Ang II-treated cardiomyocytes. LARP1 overexpression alleviated Ang II-induced cardiac remodeling, as evidenced by reduced cardiomyocyte size, fibrosis, and normalized expression of hypertrophy markers. In vivo, LARP1 overexpression improved cardiac function and reduced pathological changes in Ang II-treated mice. ATP2A2 was identified as a downstream target of LARP1, with LARP1 overexpression enhancing ATP2A2 mRNA stability and expression. Furthermore, ATP2A2 overexpression reversed hypertrophic and fibrotic changes in LARP1-deficient cardiomyocytes and mice, underscoring its critical role in mediating LARP1 protective effects.</p><p><strong>Conclusions: </strong>LARP1 alleviates Ang II-induced cardiac remodeling in vivo and in vitro, potentially by stabilizing ATP2A2 mRNA and enhancing its expression, thereby reducing pathological remodeling. These findings establish LARP1 as a promising therapeutic target for preventing cardiac remodeling and highlight ATP2A2 as a key mediator of its protective effects. Future studies should explore the therapeutic potential of LARP1-based interventions in cardiovascular disease.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"143"},"PeriodicalIF":6.2,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12541941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145349529","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":"Trim7 aggravates ischemic stroke-associated ferroptosis by promoting ubiquitin-mediated degradation of HSPA5.","authors":"Wenxuan Lu, Sha Hu, Wenhui Zhang, Ruiqiang Wang, Dongxu Zhao, Peng Ji, Peng Zhang, Yilin Zhang, Huili Gao, Ziliang Wang, Tianxiao Li, Zhigang Lu, Zhaoshuo Li","doi":"10.1186/s13578-025-01476-w","DOIUrl":"10.1186/s13578-025-01476-w","url":null,"abstract":"<p><strong>Objective: </strong>Ischemic stroke is a leading cause of neurological disability and death worldwide, posing a substantial threat to human health. Tripartite motif-containing protein 7 (Trim7), an E3 ubiquitin ligase, is involved in the progression of various diseases, but its role in ischemic stroke remains unknown. This study aims to investigate the functional significance and molecular mechanism of Trim7 in ischemia-induced neuronal injury.</p><p><strong>Methods: </strong>Trim7 knockout mice underwent transient middle cerebral artery occlusion-reperfusion, and adenovirus-mediated Trim7 knockdown or overexpression was performed in rat primary cortical neurons subjected to oxygen-glucose deprivation/reoxygenation. Ferroptosis markers, redox status, and neuronal injury were systematically evaluated. The interaction between Trim7 and heat shock protein family member A5 (HSPA5) was examined using co-immunoprecipitation, GST pull-down, and ubiquitination assays.</p><p><strong>Results: </strong>Trim7 protein was significantly upregulated in cerebral ischemia-reperfusion models. Trim7 deletion or knockdown alleviated neuronal injury, reduced lipid peroxidation and inflammation, and restored glutathione peroxidase 4 (GPX4) protein expression and activity, thereby suppressing ferroptosis. In contrast, Trim7 overexpression exacerbated ferroptotic and inflammatory responses. Mechanistically, Trim7 directly interacted with HSPA5 via its PRY/SPRY domain and the substrate-binding domain of HSPA5, and promoted K48-linked polyubiquitination of HSPA5, leading to its proteasome-dependent degradation.</p><p><strong>Conclusion: </strong>This study is the first to identify the Trim7-HSPA5-GPX4 axis as a previously unrecognized regulatory pathway that promotes ischemic-reperfusion nuernoal injury through ferroptosis. These findings provide novel mechanistic insights into the pathogenesis and potential therapeutic strategies of ischemic stroke.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"142"},"PeriodicalIF":6.2,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12542018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145349445","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":"sRAGE inhibits myocardial ischemia/reperfusion injuries via regulating Treg cells.","authors":"Jian Liu, Jie Zhang, Jing Chang, Lu Chen, Hongxia Wang, Yu Liu, Mingcong Huang, Xiangjun Zeng, Caixia Guo","doi":"10.1186/s13578-025-01482-y","DOIUrl":"10.1186/s13578-025-01482-y","url":null,"abstract":"<p><strong>Background: </strong>Regulatory T cells (Tregs) have been documented to accumulate in damaged myocardial tissue, where they play a pivotal role in attenuating excessive inflammatory responses during myocardial ischemia/reperfusion (I/R) injury. Concurrently, soluble receptor for advanced glycation end-products (sRAGE) has been demonstrated to alleviate myocardial I/R injury by suppressing inflammation, suggesting a potential involvement of Tregs in the inhibitory effects of sRAGE on myocardial I/R injury.</p><p><strong>Methods: </strong>I/R surgery or glucose deprivation/reoxygenation was employed to explore myocardial injury and the related mechanisms by using cardiomyocyte-specific sRAGE knock-in mice or cultured cardiomyocytes. Potential molecular mechanisms were analyzed via western blotting, immunohistochemistry, and flow cytometric analysis.</p><p><strong>Results: </strong>The findings revealed that sRAGE overexpression significantly increased the numbers of Tregs. Depletion of Tregs abrogated the protective effects of sRAGE against I/R-induced cardiac dysfunction, myocardial fibrosis, and inflammatory response in cardiac-specific sRAGE transgenic mice. Mechanistically, sRAGE was found to enhance the expression of programmed cell death ligand 1 (PD-L1) and its upstream JAK2/STAT3 signaling axis, thereby facilitating CD4⁺ T cells differentiation into Tregs within myocardial tissue during I/R.</p><p><strong>Conclusions: </strong>The study demonstrated that sRAGE protected against myocardial I/R injury by modulating the differentiation of Tregs through upregulation of the JAK2/STAT3-PD-L1 signaling pathway.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"144"},"PeriodicalIF":6.2,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12542090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145349530","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":"CircCdh7 induces astrogliosis and neuroinflammation to trigger hypertensive effects in the rostral ventrolateral medulla.","authors":"Shuai Zhang, Tengteng Dai, Bingjie Zhao, Xueping Wang, Linping Wang, Lei Tong, Qiangcheng Zeng, Qing He, Haili Zhang, Dongshu Du","doi":"10.1186/s13578-025-01480-0","DOIUrl":"10.1186/s13578-025-01480-0","url":null,"abstract":"<p><strong>Background: </strong>The rostral ventrolateral medulla (RVLM) is a critical vasomotor center that plays a pivotal role in the pathogenesis of hypertension. However, the involvement of circular RNAs (circRNAs) in this nucleus in blood pressure (BP) regulation remains incompletely understood.</p><p><strong>Methods: </strong>In this study, we investigated functional circRNAs in the RVLM associated with hypertension and elucidated their underlying mechanisms using multiple experimental approaches, including RNA sequencing (RNA-seq), primary cell culture, and intra-RVLM microinjection.</p><p><strong>Results: </strong>Our results revealed a significantly elevated level of the highly conserved circCdh7 in the RVLM of spontaneously hypertensive rats (SHRs). Downregulation of circCdh7 in the RVLM reduced neuronal excitability, sympathetic outflow, and BP in SHRs. Mechanistically, circCdh7 functioned as a sponge for miR-346. miR-346 knockdown largely abolished the inhibitory effects of circCdh7 suppression on RVLM astrogliosis and neuroinflammation. Furthermore, miR-346 was found to target Osmr. Overexpression of miR-346 attenuated RVLM astrogliosis and neuroinflammation, but these beneficial effects were abolished by Osmr overexpression.</p><p><strong>Conclusions: </strong>Collectively, our findings demonstrate that elevated circCdh7 expression in the RVLM drives hypertension progression, with the circCdh7/miR-346/Osmr axis serving as a key regulatory mechanism. Targeting circCdh7 may represent a promising therapeutic strategy for hypertension.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"141"},"PeriodicalIF":6.2,"publicationDate":"2025-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12536531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145330693","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}