The Involvement of miR-29b-3p in Arterial Calcification by Targeting Matrix Metalloproteinase-2.
Vascular calcification is a risk predictor and common pathological change in cardiovascular diseases that are associated with elastin degradation and phenotypic transformation of vascular smooth muscle cells via gelatinase matrix metalloproteinase-2 (MMP2). However, the mechanisms involved in this process remain unclear. In this study, we investigated the relationships between miR-29b-3p and MMP2, to confirm miR-29b-3p-mediated MMP2 expression at the posttranscriptional level in arterial calcification. In male Sprague Dawley rats, arterial calcification was induced by subcutaneous injection of a toxic dose of cholecalciferol. In vivo, the quantitative real-time polymerase chain reaction (qRT-PCR) showed that MMP2 expression was upregulated in calcified arterial tissues, and miR-29b-3p expression was downregulated. There was a negative correlation between MMP2 mRNA expression and miR-29b-3p levels (P= 0.0014,R2= 0.481). Western blotting showed that MMP2 expression was significantly increased in rats treated with cholecalciferol. In vitro, overexpression of miR-29b-3p led to decreased MMP2 expression in rat vascular smooth muscle cells, while downregulation of miR-29b-3p expression led to increased MMP2 expression. Moreover, the luciferase reporter assay confirmed that MMP2 is the direct target of miR-29b-3p. Together, our results demonstrated that a role of miR-29b-3p in vascular calcification involves targeting MMP2.
Department of Vascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
Wenhong
W
Jiang
Department of Vascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
Zhanman
Z
Zhang
Department of Vascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
Han
H
Yang
Department of Vascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
Qiuning
Q
Lin
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
Chuangye
C
Han
Department of Vascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
Xiao
0000-0002-2161-0735
X
Qin
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology; D001483:Base Sequence; D002762:Cholecalciferol / Q000494:pharmacology; D004195:Disease Models, Animal; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D014162:Transfection; D061205:Vascular Calcification / Q000201:enzymology* / Q000473:pathology
C526366:MIRN29 microRNA, rat; D035683:MicroRNAs; D002762:Cholecalciferol; D020778:Matrix Metalloproteinase 2