title: MicroRNA-34b/c inhibits aldosterone-induced vascular smooth muscle cell calcification via a SATB2/Runx2 pathway.
abstract: Increasing evidence shows that aldosterone and specific microRNAs (miRs) contribute to vascular smooth muscle cell (VSMC) calcification. In this study, we aim to explore the mechanistic links between miR-34b/c and aldosterone in VSMC calcification. VSMC calcification models were established both in vitro and in vivo. First, the levels of aldosterone, miR-34b/c and special AT-rich sequence-binding protein 2 (SATB2) were measured. Then, miR-34b/c mimics or inhibitors were transfected into VSMCs to evaluate the function of miR-34b/c. Luciferase reporter assays were used to demonstrate whether SATB2 was a direct target of miR-34b/c. Aldosterone and SATB2 were found to be markedly upregulated during VSMC calcification, whereas miR-34b/c expression was downregulated. Treatment with the mineralocorticoid receptor (MR) antagonist eplerenone inhibited VSMC calcification. In aldosterone-induced VSMC calcification, miR-34b/c levels were downregulated and SATB2 protein was upregulated. Furthermore, miR-34b/c overexpression alleviated aldosterone-induced VSMC calcification as well as inhibited the expression of SATB2 protein, whereas miR-34b/c inhibition markedly enhanced VSMC calcification and upregulated SATB2 protein. In addition, luciferase reporter assays showed that SATB2 is a direct target of miR-34b/c in VSMCs. Overexpression of SATB2 induced Runx2 overproduction and VSMC calcification. Therefore, miR-34b/c participates in aldosterone-induced VSMC calcification via a SATB2/Runx2 pathway. As miR-34b/c appears to be a negative regulator, it has potential as a therapeutic target of VSMC calcification.
authors: Department of Nephropathy and Hemodialysis, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People's Republic of China.
authors: Jianbing
authors: J
authors: Hao
authors: Department of Nephropathy and Hemodialysis, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People's Republic of China.
authors: Lei
authors: L
authors: Zhang
authors: Department of Nephropathy and Hemodialysis, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People's Republic of China.
authors: Guangting
authors: G
authors: Cong
authors: Department of Nephropathy and Hemodialysis, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People's Republic of China.
authors: Liansheng
authors: L
authors: Ren
authors: Department of Nephropathy and Hemodialysis, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, People's Republic of China. hao_lirong@163.com.
authors: Lirong
authors: L
authors: Hao
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001483:Base Sequence; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D005994:Glycerophosphates / Q000494:pharmacology; D008297:Male; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014511:Uremia / Q000150:complications / Q000235:genetics; D061205:Vascular Calcification / Q000150:complications / Q000235:genetics* / Q000473:pathology
chemical_list: D020413:3' Untranslated Regions; D050659:Core Binding Factor Alpha 1 Subunit; D005994:Glycerophosphates; C560944:MIRN34 microRNA, rat; D036961:Matrix Attachment Region Binding Proteins; D035683:MicroRNAs; D018161:Receptors, Mineralocorticoid; C586446:SATB2 protein, rat; D014157:Transcription Factors; D000450:Aldosterone; C031463:beta-glycerophosphoric acid
keywords: Aldosterone; SATB2; Vascular calcification; Vascular smooth muscle cell; miR-34b/c