miR-21 enhances cardiac fibrotic remodeling and fibroblast proliferation via CADM1/STAT3 pathway.
Cardiac fibrosis play a key role in the atrial fibrillation pathogenesis but the underlying potential molecular mechanism is still understood. However, potential mechanisms for miR-21 upregulation and its role in cardiac fibrosis remain unclear. The controls cell proliferation and processes fundamental to disease progression.



In this study, immunohistochemistry, real-time RT-PCR, cell transfection, cell cycle, cell proliferation and Western blot were used, respectively.



Here we have been demonstrated that the tumor suppressor cell adhesion molecule 1 (CADM1) is the potential target of miR-21. Our study revealed that miR-21 regulation of CADM1 expression, which was decreased in cardiac fibroblasts and fibrosis tissue. The cardiac fibroblasts transfected with miR-21 mimic promoted miR-21 overexpression enhanced STAT3 expression and decreased CADM1 expression. Nevertheless, the cardiac fibroblasts transfected with miR-21 inhibitor obtained the opposite expression result. Furthermore, downexpression of miR-21 suppressed cardiac fibroblast proliferation.



These results suggested that miR-21 overexpression promotes cardiac fibrosis via STAT3 signaling pathway by decrease CADM1 expression, indicating miR-21 as an important signaling molecule for cardiac fibrotic remodeling and AF.
Department of Cardiology, The first Hospital of Anhui Medical University, Hefei, 230031, China.|Department of Cardiothoracic Surgery, The Second Hospital of Anhui Medical University, Hefei, 230601, China.
Wei
W
Cao
Department of Cardiothoracic Surgery, The Second Hospital of Anhui Medical University, Hefei, 230601, China.
Peng
P
Shi
Department of Cardiology, The first Hospital of Anhui Medical University, Hefei, 230031, China. ttggtgtg123@163.com.|Department of Cardiology, The first Hospital of Anhui Medical University, Ji-Xi Road, Hefei, Anhui Province, 230032, China. ttggtgtg123@163.com.
Jian-Jun
JJ
Ge
D000328:Adult; D000818:Animals; D000831:Animals, Newborn; D001281:Atrial Fibrillation / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis; D005786:Gene Expression Regulation; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D020257:Ventricular Remodeling
C403514:CADM1 protein, human; C465040:Cadm1 protein, rat; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494088:Stat3 protein, rat; C546082:mirn21 microRNA, rat
CADM1; Cardiac fibroblast; Cardiac fibrosis; MicroRNA-21; STAT3