MicroRNA-155 regulates angiotensin II type 1 receptor expression and phenotypic differentiation in vascular adventitial fibroblasts.
MicroRNAs (miRNAs), which are genomically encoded small RNAs, negatively regulate target gene expression at the post-transcriptional level. Our recent study indicated that microRNA-155 (miR-155) might be negatively correlated with blood pressure, and it has been suggested that miR-155-mediated target genes could be involved in the cardiovascular diseases. Bioinformatic analyses predict that angiotensin II type 1 receptor (AT(1)R) is a miR-155 target gene. The present study investigated the potential role of miR-155 in regulating AT(1)R expression and phenotypic differentiation in rat aortic adventitial fibroblasts (AFs). Luciferase assay demonstrated that miR-155 suppressed AT(1)R 3'-UTR reporter construct activity. miR-155 overexpression in AFs did not reduce target mRNA levels, but significantly reduced target protein expression. In addition, AFs transfected with pSUPER/miR-155 exhibited reduced Ang II-induced ERK1/2 activation. miR-155 overexpression in cells attenuated Ang II-induced α-smooth muscle actin (α-SMA, produces myofibroblast) expression, but did not transform growth factor beta-1 (TGF-β1). This study demonstrated that miR-155 could have an important role in regulating adventitial fibroblast differentiation and contribute to suppression of AT(1)R expression.
Zheng
Liang
L
State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Vascular Biology and Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China.
Xu
Chan-Chan
CC
Chen
Wen-Dong
WD
Shen
Wei-Li
WL
Ruan
Cheng-Chao
CC
Zhu
Li-Min
LM
Zhu
Ding-Liang
DL
Gao
Ping-Jin
PJ
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D015536:Down-Regulation; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D005786:Gene Expression Regulation; D006973:Hypertension / Q000235:genetics*; D008156:Luciferases / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*
D035683:MicroRNAs; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D008156:Luciferases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3