Cellular signalling最新文献_第9页

IRF1 regulates autophagy and microglia polarization in retinal ischemia-reperfusion through NCOA1/Wnt/β-catenin signalling pathway IRF1通过NCOA1/Wnt/β-catenin信号通路调控视网膜缺血-再灌注过程中的自噬和小胶质细胞极化

IF 4.4 2区生物学

Cellular signalling Pub Date : 2025-03-15 DOI: 10.1016/j.cellsig.2025.111746

Di Yang , Jian-shu Kang , Hua Zhong , Hong-mei Liu , Shen Nian , Kai-xiong Qing

{"title":"IRF1 regulates autophagy and microglia polarization in retinal ischemia-reperfusion through NCOA1/Wnt/β-catenin signalling pathway","authors":"Di Yang , Jian-shu Kang , Hua Zhong , Hong-mei Liu , Shen Nian , Kai-xiong Qing","doi":"10.1016/j.cellsig.2025.111746","DOIUrl":"10.1016/j.cellsig.2025.111746","url":null,"abstract":"<div><h3>Background</h3><div>Interferon regulatory factor 1 (IRF1) is an important regulatory factor in the development of eyes, and it has been proved to be involved in the regulation of ischemia-reperfusion process. But its role in retinal ischemia-reperfusion (RIR) remains unclear.</div></div><div><h3>Methods</h3><div>RIR rat model was induced by increasing intraocular pressure. Hematoxylin and eosin (HE) staining, immunofluorescence (IF) staining, and western blot experiments were used to explore the levels of IRF1, autophagy, and microglia polarization in RIR. Western blot, transmission electron microscope, IF, and ELISA assays were used to explore the effects of IRF1, Nuclear receptor coactivator 1 (NCOA1), and Wnt/β-catenin signalling pathways in OGD/R-induced autophagy and polarization of rat retinal microglia. CHIP and dual-luciferase experiments verify the interaction between IRF1 and NCOA1. CHIP and dual-luciferase experiments were used to verify the interaction between IRF1 and NCOA1. Adeno-associated viruses interfering with IRF1 and NCOA1 were injected into the vitreous of rats to explore the functions of IRF1 and NCOA1 in RIR rats.</div></div><div><h3>Results</h3><div>IRF1 and M1-type markers of microglia in retina of RIR rats increased, and autophagy level decreased. Knockdown of IRF1 and NCOA1 increased autophagy of OGD/R-induced retinal microglia, inhibited M1-type polarization and inflammatory cytokines, alleviated RIR injury in rats, and inhibited the activation of Wnt/β-catenin signalling pathway. The Wnt/β-catenin signalling pathway activator HLY78 partially reversed the effect of knocking down NCOA1 on retinal microglia. Mechanically, knockdown of IRF1 inhibited the activation of Wnt/β-catenin signalling pathway by inhibiting the transcription of NCOA1.</div></div><div><h3>Conclusion</h3><div>Inhibition of IRF1 has a protective effect on RIR damage by regulating NCOA1/Wnt/β-catenin signalling pathway.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"131 ","pages":"Article 111746"},"PeriodicalIF":4.4,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143643932","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}

引用次数: 0

OTUB1 promotes glioma progression by stabilizing TRAF4 OTUB1通过稳定TRAF4促进胶质瘤进展。

IF 4.4 2区生物学

Cellular signalling Pub Date : 2025-03-14 DOI: 10.1016/j.cellsig.2025.111704

Hongjun Liu , Shasha Tan , Zhou Li , Jian Qi , Xiaoping Tang , Junhao Zhang

{"title":"OTUB1 promotes glioma progression by stabilizing TRAF4","authors":"Hongjun Liu , Shasha Tan , Zhou Li , Jian Qi , Xiaoping Tang , Junhao Zhang","doi":"10.1016/j.cellsig.2025.111704","DOIUrl":"10.1016/j.cellsig.2025.111704","url":null,"abstract":"<div><h3>Background</h3><div>Glioma is a highly heterogeneous brain tumor with poor prognosis. This study aims to investigate the functional role of OTUB1 in glioma and its impact on TRAF4 stability, seeking potential therapeutic targets.</div></div><div><h3>Methods</h3><div>We mined single-cell sequencing data from 12 glioma patients to analyze the heterogeneity of 20,145 glioma cells. The expression of OTUB1 in glioma tissues and cell lines was assessed using Western blot and qPCR. Additionally, immunoprecipitation and ubiquitination assays were conducted to evaluate the effect of OTUB1 on TRAF4 and its role in regulating TRAF4 stability. In vitro assays were performed to assess the effects of OTUB1 on cell proliferation, migration, and clonogenicity, while in vivo experiments using xenograft models in nude mice validated the impact of OTUB1 on tumor growth.</div></div><div><h3>Results</h3><div>OTUB1 was found to be significantly overexpressed in glioma tissues, correlating with poor patient outcomes. Knockdown of OTUB1 markedly inhibited the proliferation and migration of LN229 and U87MG cells while increasing apoptosis. Immunoprecipitation studies revealed that OTUB1 stabilizes TRAF4 by inhibiting its ubiquitination, thereby promoting glioma cell proliferation and invasion. In vivo, tumors with OTUB1 knockdown demonstrated significantly reduced growth rates.</div></div><div><h3>Conclusion</h3><div>OTUB1 plays a critical role in glioma progression and may serve as a novel therapeutic target. The development of inhibitors targeting OTUB1 could potentially improve outcomes for glioma patients.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"131 ","pages":"Article 111704"},"PeriodicalIF":4.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639580","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}

引用次数: 0

Protein succinylation mechanisms and potential targeted therapies in urinary disease 尿路疾病的蛋白琥珀酰化机制和潜在的靶向治疗。

IF 4.4 2区生物学

Cellular signalling Pub Date : 2025-03-14 DOI: 10.1016/j.cellsig.2025.111744

Yuanquan Lou , Caitao Dong , Qinhong Jiang, Ziqi He, Sixing Yang

{"title":"Protein succinylation mechanisms and potential targeted therapies in urinary disease","authors":"Yuanquan Lou , Caitao Dong , Qinhong Jiang, Ziqi He, Sixing Yang","doi":"10.1016/j.cellsig.2025.111744","DOIUrl":"10.1016/j.cellsig.2025.111744","url":null,"abstract":"<div><div>Succinylation is a relatively common post-translational modification. It occurs in the cytoplasm, mitochondria, and the nucleus, where its essential precursor, succinyl-CoA, is present, allowing for the modification of non-histone and histone proteins. In normal cells, succinylation levels are carefully regulated to sustain a dynamic balance, necessitating the involvement of various regulatory mechanisms, including non-enzymatic reactions, succinyltransferases, and desuccinylases. Among these regulatory factors, sirtuin 5, the first identified desuccinylase, plays a significant role and has been extensively researched. The level of succinylation has a significant effect on multiple metabolic pathways, including the tricarboxylic acid cycle, redox balance, and fatty acid metabolism. Dysregulated succinylation can contribute to the progression or exacerbation of various urinary diseases. Succinylation predominantly affects disease progression by altering the expression of key genes and modulating the activity of enzymes involved in vital metabolic processes. Desuccinylases primarily affect enzymes associated with Warburg's effect, thereby affecting the energy supply of tumor cells, while succinyltransferases can regulate gene transcription to alter cell phenotype, thereby involving the development of urinary diseases. Considering these effects, targeting succinylation-related enzymes to regulate metabolic pathways or gene expression may offer a promising therapeutic strategy for treating urinary diseases.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"131 ","pages":"Article 111744"},"PeriodicalIF":4.4,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639583","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}

引用次数: 0

The KSR1/MEK/ERK signaling pathway promotes the progression of intrauterine adhesions KSR1/MEK/ERK信号通路促进宫内粘连的进展。

IF 4.4 2区生物学

Cellular signalling Pub Date : 2025-03-13 DOI: 10.1016/j.cellsig.2025.111730

Shasha Wu , Qiuhong Chen , Xiao Yang , Lulu Zhang , Xiyue Huang , Jinglin Huang , Jiangling Wu , Congcong Sun , Wenwen Zhang , Jia Wang

{"title":"The KSR1/MEK/ERK signaling pathway promotes the progression of intrauterine adhesions","authors":"Shasha Wu , Qiuhong Chen , Xiao Yang , Lulu Zhang , Xiyue Huang , Jinglin Huang , Jiangling Wu , Congcong Sun , Wenwen Zhang , Jia Wang","doi":"10.1016/j.cellsig.2025.111730","DOIUrl":"10.1016/j.cellsig.2025.111730","url":null,"abstract":"<div><div>Kinase suppressor of Ras 1 (KSR1) serves as a scaffold protein within the RAS-RAF pathway and plays a role in tumorigenesis, immune regulation, cell proliferation, and apoptosis. However, the specific role of KSR1 in the formation and progression of fibrotic diseases, such as intrauterine adhesions (IUA), remains unclear. This study aims to investigate KSR1 expression in IUA and the mechanisms underlying its role in promoting IUA progression. KSR1 was found to be significantly overexpressed in the endometrium of both IUA model rats and patients with IUA. KSR1 is positively involved in the regulation of proliferation, migration, and fibrosis (FN1, Collagen I, α-SMA) in immortalized human endometrial stromal cells (THESCs). Furthermore, KSR1 knockdown was observed to inhibit the fibrosis, proliferation, and migration of transforming growth factor-β1 (TGF-β1)-induced THESCs. Further studies demonstrated that the key proteins of the MEK/ERK signaling pathway, p-MEK1 and p-ERK1/2, were significantly overexpressed in the uterus of IUA rats. In vitro rescue experiments confirmed that the MEK/ERK pathway inhibitor U0126 (An ERK inhibitor) effectively suppressed the enhanced fibrosis, proliferation, and migration induced by KSR1 overexpression. In conclusion, this study demonstrates that KSR1 promotes IUA by enhancing proliferation, migration, and fibrosis of endometrial stromal cells via the MEK/ERK signaling pathway.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"131 ","pages":"Article 111730"},"PeriodicalIF":4.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633886","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}

引用次数: 0

Modulation of Mettl5 alleviates airway allergy by regulating the epigenetic profile of M2 macrophages 调节Mettl5通过调节M2巨噬细胞的表观遗传谱减轻气道过敏

IF 4.4 2区生物学

Cellular signalling Pub Date : 2025-03-13 DOI: 10.1016/j.cellsig.2025.111740

Haoyue Zheng , Yixuan Dong , Xiwen Zhang , Jiangqi Liu , Xiaorui Geng , Zhiqiang Liu , Yun Liao , Yu Liu , Pingchang Yang , Gui Yang , Xiaoyu Liu

{"title":"Modulation of Mettl5 alleviates airway allergy by regulating the epigenetic profile of M2 macrophages","authors":"Haoyue Zheng , Yixuan Dong , Xiwen Zhang , Jiangqi Liu , Xiaorui Geng , Zhiqiang Liu , Yun Liao , Yu Liu , Pingchang Yang , Gui Yang , Xiaoyu Liu","doi":"10.1016/j.cellsig.2025.111740","DOIUrl":"10.1016/j.cellsig.2025.111740","url":null,"abstract":"<div><div>M2 macrophages (M2 cells) are known to be involved in both Th2 responses and immune regulation. However, the underlying mechanisms remain unclear. Functional abnormalities in macrophages are associated with airway allergy (AA). The objective of this study was to investigate the role of methyltransferase-like 5 (Mettl5) in macrophages and its potential to alleviate AA. In this study, an airway allergy (AA) mouse model was established using dust mite extracts (DME) as the specific antigen. M2 cells were collected from mice with and without AA. The role of Mettl5 in modulating the immune activities of M2 cells was assessed using both epigenetic and immunological approaches. We found that Mettl5 levels were elevated in airway M2 cells from mice with AA. The presence of Mettl5 in airway M2 cells was positively correlated with airway Th2 polarization in these mice. Airway M2 cells from AA mice exhibited impaired immune-suppressive function, which was resolved by ablating the Mettl5 gene in macrophages. Mettl5 was responsible for the hypermethylation of the <em>Il10</em> promoter in airway M2 cells of AA mice. Exposure to DME induced Mettl5, which in turn recruited USP21 to deubiquitinate GATA3, thereby boosting IL-4 expression in M2 cells. Inhibiting Mettl5 restored the immune-suppressive capacity of airway M2 cells and mitigated experimental AA. In conclusion, Mettl5 plays a critical role in subverting the immune-regulatory capacity and enhancing IL-4 expression in M2 cells. Inhibition of Mettl5 can mitigate experimental AA by restoring the immune-regulatory functions of M2 cells.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"131 ","pages":"Article 111740"},"PeriodicalIF":4.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628660","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}

引用次数: 0

Neurodegenerative diseases: Epigenetic regulatory mechanisms and therapeutic potential 神经退行性疾病：表观遗传调控机制和治疗潜力

IF 4.4 2区生物学

Cellular signalling Pub Date : 2025-03-13 DOI: 10.1016/j.cellsig.2025.111715

Jianbing Men , Xinyue Wang , Yunnuo Zhou , Yumeng Huang , Yue Zheng , Yingze Wang , Shuang Yang , Nan Chen , Nan Yan , Xiaoxu Duan

{"title":"Neurodegenerative diseases: Epigenetic regulatory mechanisms and therapeutic potential","authors":"Jianbing Men , Xinyue Wang , Yunnuo Zhou , Yumeng Huang , Yue Zheng , Yingze Wang , Shuang Yang , Nan Chen , Nan Yan , Xiaoxu Duan","doi":"10.1016/j.cellsig.2025.111715","DOIUrl":"10.1016/j.cellsig.2025.111715","url":null,"abstract":"<div><div>Neurodegenerative diseases (NDDs) are a class of diseases in which the progressive loss of subtype-specific neurons leads to dysfunction. NDDs include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), among others. Previous studies have demonstrated that the pathogenesis of NDDs involves various mechanisms, including genetic factors, oxidative stress, apoptosis, and the immune response. Recent studies have shown that epigenetic regulation mediates the interactions between DNA methylation, chromatin remodeling, histone modification, and non-coding RNAs, thus affecting gene transcription. A growing body of research links epigenetic modifications to crucial pathways involved in the occurrence and development of NDDs. Epigenetics has also been found to regulate and maintain nervous system function, and its imbalance is closely related to the occurrence and development of NDDs. The present review summarizes focuses on the role of epigenetic modifications in the pathogenesis of NDDs and provides an overview of the key genes regulated by DNA methylation, histone modification, and non-coding RNAs in NDDs. Further, the current research status of epigenetics in NDDs is summarized and the potential application of epigenetics in the clinical diagnosis and treatment of NDDs is discussed.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"131 ","pages":"Article 111715"},"PeriodicalIF":4.4,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629397","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}

引用次数: 0

Mechanical stretch promotes the neutrophil recruitment potential of fibroblasts through the Piezo/NFAT1/LIF axis 机械拉伸通过Piezo/NFAT1/LIF轴促进成纤维细胞的中性粒细胞募集潜能

IF 4.4 2区生物学

Cellular signalling Pub Date : 2025-03-12 DOI: 10.1016/j.cellsig.2025.111718

Yi Zhou , Weihao Zhang , Jiajie Lin , Yipeng Zeng , Zhikun Li , Peng Wang , Jinteng Li , Wenhui Yu , Zepeng Su , Zipeng Xiao , Guozhen Shen , Yanfeng Wu , Huiyong Shen , Zhongyu Xie

{"title":"Mechanical stretch promotes the neutrophil recruitment potential of fibroblasts through the Piezo/NFAT1/LIF axis","authors":"Yi Zhou , Weihao Zhang , Jiajie Lin , Yipeng Zeng , Zhikun Li , Peng Wang , Jinteng Li , Wenhui Yu , Zepeng Su , Zipeng Xiao , Guozhen Shen , Yanfeng Wu , Huiyong Shen , Zhongyu Xie","doi":"10.1016/j.cellsig.2025.111718","DOIUrl":"10.1016/j.cellsig.2025.111718","url":null,"abstract":"<div><div>The entheses are the sites where tendons or ligaments insert into osseous structures and play a crucial role in transmitting mechanical stress from muscles to bones. Under excessive mechanical loads, the entheses may sustain inflammation, leading to isolated enthesitis. However, the specific mechanisms through which enthesitis occurs have not yet been fully elucidated. In our study, we discovered that mechanical stress is a critical factor that drives fibroblasts to recruit neutrophils through the secretion of leukemia inhibitory factor (LIF). Further research revealed that fibroblasts convert mechanical stress, a physical signal, into a chemical signal through the Piezo mechanosensitive ion channel, subsequently activating the transcription factor NFAT1 and upregulating LIF expression. This study not only helps elucidate the mechanisms underlying the development of enthesitis but also offers potential insights into the clinical management and treatment of patients with enthesitis.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"131 ","pages":"Article 111718"},"PeriodicalIF":4.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628661","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}

引用次数: 0

OTUB1 promotes the progression of acute myeloid leukemia by regulating glycolysis via deubiquitinating c-Myc OTUB1通过去泛素化c-Myc来调节糖酵解，从而促进急性髓系白血病的进展

IF 4.4 2区生物学

Cellular signalling Pub Date : 2025-03-11 DOI: 10.1016/j.cellsig.2025.111735

Yang Liao , Liang Zhong , Yi Zhao , Peng Wan , Ying Zhang , Ying Deng , Hongyan Zhang , Meng Wang , Beizhong Liu

{"title":"OTUB1 promotes the progression of acute myeloid leukemia by regulating glycolysis via deubiquitinating c-Myc","authors":"Yang Liao , Liang Zhong , Yi Zhao , Peng Wan , Ying Zhang , Ying Deng , Hongyan Zhang , Meng Wang , Beizhong Liu","doi":"10.1016/j.cellsig.2025.111735","DOIUrl":"10.1016/j.cellsig.2025.111735","url":null,"abstract":"<div><div>Acute myeloid leukemia (AML) is the most common type of adult leukemia and patients with AML often have poor prognosis, for which there remains an urgent need to identify novel selective targeted therapy. OTUB1, a deubiquitinating enzyme, is associated with the malignant progression of multiple cancers. However, the role of OTUB1 in AML is still unclear and warrants further investigations. Our study revealed that the expression of OTUB1 is significantly upregulated in AML. Next, we observed that knockdown of OTUB1 inhibits AML cell proliferation and promotes AML cell apoptosis and G0/G1 phase blockade using CCK-8 assay, western blotting, and flow cytometry. Mechanistically, OTUB1 drives the malignant development of AML through regulating cellular aerobic glycolysis by deubiquitinating c-Myc. Lastly, by investigating whether inhibition of OTUB1 enhances the sensitivity of chemotherapeutic agents commonly used in the clinical treatment of AML, we found that combining OTUB1 inhibition with daunorubicin treatment could achieve better therapeutic effects in AML. In brief, our results revealed a novel mechanism by which OTUB1 promotes glycolysis via deubiquitinating c-Myc in AML. Consequently, targeting OTUB1 may provide a promising strategy for enhancing the efficacy of AML treatment.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"131 ","pages":"Article 111735"},"PeriodicalIF":4.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620365","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}

引用次数: 0

Inhibition of N6-methyladenosine methylation of ASC by berberine ameliorates pyroptosis of renal tubular epithelial cells in acute kidney injury 小檗碱抑制ASC n6 -甲基腺苷甲基化可改善急性肾损伤肾小管上皮细胞的焦亡。

IF 4.4 2区生物学

Cellular signalling Pub Date : 2025-03-11 DOI: 10.1016/j.cellsig.2025.111732

Jiacheng Li , Linxiao Lv , Mingyang Hu , Zhangsuo Liu , Sijie Zhou

{"title":"Inhibition of N6-methyladenosine methylation of ASC by berberine ameliorates pyroptosis of renal tubular epithelial cells in acute kidney injury","authors":"Jiacheng Li , Linxiao Lv , Mingyang Hu , Zhangsuo Liu , Sijie Zhou","doi":"10.1016/j.cellsig.2025.111732","DOIUrl":"10.1016/j.cellsig.2025.111732","url":null,"abstract":"<div><div>Acute kidney injury (AKI) lacks a definitive therapeutic approach beyond supportive care. One significant pathological mechanism involves the regulated death of tubular epithelial cells; however, the regulatory mechanisms underlying this cell death pathway require further investigation. The N6-methyladenosine (m6A) modification, recognized as the most prevalent modification in eukaryotes, plays a critical role in the regulatory processes associated with AKI. Here, this study investigates the association between methyltransferase-like 3 (METTL3) and pyroptosis in mice with folic acid (FA)-induced AKI. Both in vitro and in vivo experiments have confirmed that METTL3 plays a role in AKI progression, correlating with renal epithelial cell pyroptosis and inflammation. Moreover, RNA immunoprecipitation quantitative PCR (RIP-qPCR) analysis demonstrated that METTL3-mediated m6A methylation occurred in the mRNA of Apoptosis-associated speck-like protein containing a CARD (ASC) in H<sub>2</sub>O<sub>2</sub>-induced renal tubular epithelial (TCMK-1) cells. Notably, METTL3 knockdown resulted in reduced ASC protein expression, decreased release of inflammatory factors, and reduced pyroptosis. In addition, we verified the inhibitory effect of berberine hydrochloride, a monomer used in traditional Chinese medicine, on METTL3 expression. We also demonstrated that berberine ameliorated FA-induced AKI and H<sub>2</sub>O<sub>2</sub>-induced pyroptosis in TCMK-1 cells by inhibiting METTL3 and modulating the ASC/caspase-1/Gasdermin D axis. These findings provide insights into targeted therapies and drug development for AKI.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"131 ","pages":"Article 111732"},"PeriodicalIF":4.4,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613556","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}

引用次数: 0

PP2A adapter protein IER5 induces dephosphorylation and degradation of MDM2, thereby stabilizing p53 PP2A适配蛋白IER5诱导MDM2去磷酸化和降解，从而稳定p53

IF 4.4 2区生物学

Cellular signalling Pub Date : 2025-03-11 DOI: 10.1016/j.cellsig.2025.111739

Taisei Nakada, Mayuko Koga, Hiroto Takeuchi, Kuriko Doi, Haruka Sugiyama, Hiroshi Sakurai

引用次数: 0