MicroRNA-34b/c inhibits aldosterone-induced vascular smooth muscle cell calcification via a SATB2/Runx2 pathway

• Published in: Cell and tissue research Vol. 366; no. 3; pp. 733 - 746
• Main Authors: Hao, Jianbing, Zhang, Lei, Cong, Guangting, Ren, Liansheng, Hao, Lirong
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2016; Springer; Springer Nature B.V
• Subjects: 3' Untranslated Regions - genetics; Aldosterone; Aldosterone - pharmacology; Animals; Aorta - drug effects; Base Sequence; Biomedical and Life Sciences; Biomedicine; Calcification; Calcification (Physiology); Core Binding Factor Alpha 1 Subunit - genetics; Core Binding Factor Alpha 1 Subunit - metabolism; Gene Expression Regulation - drug effects; Glucocorticoids; Glycerophosphates - pharmacology; Human Genetics; Kidneys; Luciferase; Male; Matrix Attachment Region Binding Proteins - genetics; Matrix Attachment Region Binding Proteins - metabolism; MicroRNA; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Molecular Medicine; Muscle, Smooth, Vascular - pathology; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; Myocytes, Smooth Muscle - pathology; Osteoblasts - drug effects; Osteoblasts - metabolism; Protein binding; Proteins; Proteomics; Rats, Sprague-Dawley; Receptors, Mineralocorticoid - metabolism; Regular Article; Signal Transduction - drug effects; Smooth muscle; Steroids (Organic compounds); Transcription Factors - genetics; Transcription Factors - metabolism; Uremia - complications; Uremia - genetics; Vascular Calcification - complications; Vascular Calcification - genetics; Vascular Calcification - pathology; Vascular calcification; miR-34b/c; Vascular smooth muscle cell; Aldosterone; SATB2
• DOI: 10.1007/s00441-016-2469-8
• ISSN: 0302-766X

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.