Pengxi Shi, Ao Tan, Yuanyuan Ma, Lingli Que, Chuanfu Li, Yongfeng Shao, Haoliang Sun, Yuehua Li, Jiantao Li
{"title":"MicroRNA-19a-3p 通过靶向 BAMBI 增强 TGF-β1 诱导的心脏成纤维细胞活化。","authors":"Pengxi Shi, Ao Tan, Yuanyuan Ma, Lingli Que, Chuanfu Li, Yongfeng Shao, Haoliang Sun, Yuehua Li, Jiantao Li","doi":"10.7555/JBR.37.20230313","DOIUrl":null,"url":null,"abstract":"<p><p>Myocardial fibrosis is a major pathogenic factor contributing to cardiac remodeling and heart failure. Recent research has indicated that microRNAs play a crucial role in the progression of cardiac fibrosis. Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) have been shown to alleviate myocardial fibrosis by inhibiting the transforming growth factor β1 (TGF-β1) signaling pathway. Therefore, the current study aimed to elucidate the post-transcriptional regulation of BAMBI by miR-19a-3p and its role in TGF-β1-induced cardiac fibroblast activation. We found that transverse aortic constriction induced both myocardial interstitial and perivascular collagen deposition. Quantitative reverse transcription-PCR (qRT-PCR) analysis showed that the expression level of miR-19a-3p was increased in the myocardial tissues of cardiac fibrosis, and TGF-β1 induced an upregulation in miR-19a-3p expression in cardiac fibroblasts. The dual-luciferase reporter assay and qRT-PCR verified that miR-19a-3p directly bound to the 3' untranslated regions of <i>BAMBI</i> mRNA, thereby reducing BAMBI expression and diminishing its ability to inhibit the TGF-β1 signaling pathway. Furthermore, overexpression of miR-19a-3p mimic increased the activation of TGF-β1/SMAD2/3 pathway signaling, promoting cardiac fibroblast activation. However, this activation was blocked by BAMBI overexpression. These findings imply that miR-19a-3p enhances the activation of TGF-β1/SMAD2/3 by inhibiting BAMBI, further boosting the activation of cardiac fibroblasts and contributing to myocardial fibrosis.</p>","PeriodicalId":15061,"journal":{"name":"Journal of Biomedical Research","volume":" ","pages":"171-183"},"PeriodicalIF":2.4000,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11982684/pdf/","citationCount":"0","resultStr":"{\"title\":\"miR-19a-3p enhances TGF-β1-induced cardiac fibroblast activation <i>via</i> targeting BAMBI.\",\"authors\":\"Pengxi Shi, Ao Tan, Yuanyuan Ma, Lingli Que, Chuanfu Li, Yongfeng Shao, Haoliang Sun, Yuehua Li, Jiantao Li\",\"doi\":\"10.7555/JBR.37.20230313\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Myocardial fibrosis is a major pathogenic factor contributing to cardiac remodeling and heart failure. Recent research has indicated that microRNAs play a crucial role in the progression of cardiac fibrosis. Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) have been shown to alleviate myocardial fibrosis by inhibiting the transforming growth factor β1 (TGF-β1) signaling pathway. Therefore, the current study aimed to elucidate the post-transcriptional regulation of BAMBI by miR-19a-3p and its role in TGF-β1-induced cardiac fibroblast activation. We found that transverse aortic constriction induced both myocardial interstitial and perivascular collagen deposition. Quantitative reverse transcription-PCR (qRT-PCR) analysis showed that the expression level of miR-19a-3p was increased in the myocardial tissues of cardiac fibrosis, and TGF-β1 induced an upregulation in miR-19a-3p expression in cardiac fibroblasts. The dual-luciferase reporter assay and qRT-PCR verified that miR-19a-3p directly bound to the 3' untranslated regions of <i>BAMBI</i> mRNA, thereby reducing BAMBI expression and diminishing its ability to inhibit the TGF-β1 signaling pathway. Furthermore, overexpression of miR-19a-3p mimic increased the activation of TGF-β1/SMAD2/3 pathway signaling, promoting cardiac fibroblast activation. However, this activation was blocked by BAMBI overexpression. These findings imply that miR-19a-3p enhances the activation of TGF-β1/SMAD2/3 by inhibiting BAMBI, further boosting the activation of cardiac fibroblasts and contributing to myocardial fibrosis.</p>\",\"PeriodicalId\":15061,\"journal\":{\"name\":\"Journal of Biomedical Research\",\"volume\":\" \",\"pages\":\"171-183\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2024-05-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11982684/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Biomedical Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.7555/JBR.37.20230313\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biomedical Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.7555/JBR.37.20230313","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
miR-19a-3p enhances TGF-β1-induced cardiac fibroblast activation via targeting BAMBI.
Myocardial fibrosis is a major pathogenic factor contributing to cardiac remodeling and heart failure. Recent research has indicated that microRNAs play a crucial role in the progression of cardiac fibrosis. Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) have been shown to alleviate myocardial fibrosis by inhibiting the transforming growth factor β1 (TGF-β1) signaling pathway. Therefore, the current study aimed to elucidate the post-transcriptional regulation of BAMBI by miR-19a-3p and its role in TGF-β1-induced cardiac fibroblast activation. We found that transverse aortic constriction induced both myocardial interstitial and perivascular collagen deposition. Quantitative reverse transcription-PCR (qRT-PCR) analysis showed that the expression level of miR-19a-3p was increased in the myocardial tissues of cardiac fibrosis, and TGF-β1 induced an upregulation in miR-19a-3p expression in cardiac fibroblasts. The dual-luciferase reporter assay and qRT-PCR verified that miR-19a-3p directly bound to the 3' untranslated regions of BAMBI mRNA, thereby reducing BAMBI expression and diminishing its ability to inhibit the TGF-β1 signaling pathway. Furthermore, overexpression of miR-19a-3p mimic increased the activation of TGF-β1/SMAD2/3 pathway signaling, promoting cardiac fibroblast activation. However, this activation was blocked by BAMBI overexpression. These findings imply that miR-19a-3p enhances the activation of TGF-β1/SMAD2/3 by inhibiting BAMBI, further boosting the activation of cardiac fibroblasts and contributing to myocardial fibrosis.