{"title":"SIAH1 通过调控 IκB-α/NF-κB 信号促进糖尿病心肌病中心肌细胞的脓毒症","authors":"Jinbin Wu, Yaoming Yan","doi":"10.1615/critreveukaryotgeneexpr.2024052773","DOIUrl":null,"url":null,"abstract":"Inflammation-mediated dysfunction of cardiomyocytes is the main cause of diabetic cardiomyopathy (DCM). The present study aimed to investigate the roles of SIAH1 in DCM. RT-qPCR was conducted to detect mRNA levels. ELISA was performed to detect cytokine release. Western blot was used to detect protein expression. LDH assay was used to determine cytotoxicity. In vitro ubiquitination assay was applied to determine the ubiquitination of IκB-α. TUNEL assay was conducted to determine cell death. Flow cytometry was applied for determining cardiomyocyte pyroptosis. The results showed that SIAH1 was overexpressed in human inflammatory cardiomyopathy. High expression of SIAH1 was associated with inflammatory response. SIAH1 was also overexpressed lipopolysaccharide (LPS)-induced inflammatory cardiomyopathy model in vitro. However, SIAH1 knockdown suppressed the inflammatory-related pyroptosis of cardiomyocytes. SIAH1 promoted the ubiquitination of IκB-α and activation of NF-κB signaling, which promoted the pyroptosis of cardiomyocytes. In conclusion, SIAH1 exacerbated the progression of human inflammatory cardiomyopathy via inducing the ubiquitination of IκB-α and activation of NF-κB signaling. Therefore, SIAH1/IκB-α/NF-κB signaling may be a potential target for human inflammatory cardiomyopathy.","PeriodicalId":56317,"journal":{"name":"Critical Reviews in Eukaryotic Gene Expression","volume":null,"pages":null},"PeriodicalIF":1.5000,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"SIAH1 promotes the pyroptosis of cardiomyocytes in diabetic cardiomyopathy via regulating IκB-α/NF-κB signaling\",\"authors\":\"Jinbin Wu, Yaoming Yan\",\"doi\":\"10.1615/critreveukaryotgeneexpr.2024052773\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Inflammation-mediated dysfunction of cardiomyocytes is the main cause of diabetic cardiomyopathy (DCM). The present study aimed to investigate the roles of SIAH1 in DCM. RT-qPCR was conducted to detect mRNA levels. ELISA was performed to detect cytokine release. Western blot was used to detect protein expression. LDH assay was used to determine cytotoxicity. In vitro ubiquitination assay was applied to determine the ubiquitination of IκB-α. TUNEL assay was conducted to determine cell death. Flow cytometry was applied for determining cardiomyocyte pyroptosis. The results showed that SIAH1 was overexpressed in human inflammatory cardiomyopathy. High expression of SIAH1 was associated with inflammatory response. SIAH1 was also overexpressed lipopolysaccharide (LPS)-induced inflammatory cardiomyopathy model in vitro. However, SIAH1 knockdown suppressed the inflammatory-related pyroptosis of cardiomyocytes. SIAH1 promoted the ubiquitination of IκB-α and activation of NF-κB signaling, which promoted the pyroptosis of cardiomyocytes. In conclusion, SIAH1 exacerbated the progression of human inflammatory cardiomyopathy via inducing the ubiquitination of IκB-α and activation of NF-κB signaling. Therefore, SIAH1/IκB-α/NF-κB signaling may be a potential target for human inflammatory cardiomyopathy.\",\"PeriodicalId\":56317,\"journal\":{\"name\":\"Critical Reviews in Eukaryotic Gene Expression\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2024-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Critical Reviews in Eukaryotic Gene Expression\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1615/critreveukaryotgeneexpr.2024052773\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOTECHNOLOGY & APPLIED MICROBIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Critical Reviews in Eukaryotic Gene Expression","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1615/critreveukaryotgeneexpr.2024052773","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
SIAH1 promotes the pyroptosis of cardiomyocytes in diabetic cardiomyopathy via regulating IκB-α/NF-κB signaling
Inflammation-mediated dysfunction of cardiomyocytes is the main cause of diabetic cardiomyopathy (DCM). The present study aimed to investigate the roles of SIAH1 in DCM. RT-qPCR was conducted to detect mRNA levels. ELISA was performed to detect cytokine release. Western blot was used to detect protein expression. LDH assay was used to determine cytotoxicity. In vitro ubiquitination assay was applied to determine the ubiquitination of IκB-α. TUNEL assay was conducted to determine cell death. Flow cytometry was applied for determining cardiomyocyte pyroptosis. The results showed that SIAH1 was overexpressed in human inflammatory cardiomyopathy. High expression of SIAH1 was associated with inflammatory response. SIAH1 was also overexpressed lipopolysaccharide (LPS)-induced inflammatory cardiomyopathy model in vitro. However, SIAH1 knockdown suppressed the inflammatory-related pyroptosis of cardiomyocytes. SIAH1 promoted the ubiquitination of IκB-α and activation of NF-κB signaling, which promoted the pyroptosis of cardiomyocytes. In conclusion, SIAH1 exacerbated the progression of human inflammatory cardiomyopathy via inducing the ubiquitination of IκB-α and activation of NF-κB signaling. Therefore, SIAH1/IκB-α/NF-κB signaling may be a potential target for human inflammatory cardiomyopathy.
期刊介绍:
Critical ReviewsTM in Eukaryotic Gene Expression presents timely concepts and experimental approaches that are contributing to rapid advances in our mechanistic understanding of gene regulation, organization, and structure within the contexts of biological control and the diagnosis/treatment of disease. The journal provides in-depth critical reviews, on well-defined topics of immediate interest, written by recognized specialists in the field. Extensive literature citations provide a comprehensive information resource.
Reviews are developed from an historical perspective and suggest directions that can be anticipated. Strengths as well as limitations of methodologies and experimental strategies are considered.