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MiR‐29‐mediated elastin down‐regulation contributes to inorganic phosphorus‐induced osteoblastic differentiation in vascular smooth muscle cells
Author(s) -
Sudo Ryo,
Sato Fumiaki,
Azechi Takuya,
Wachi Hiroshi
Publication year - 2015
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12311
Subject(s) - elastin , vascular smooth muscle , gene knockdown , calcification , messenger rna , pi , biology , medicine , endocrinology , gene expression , stimulation , vascular tissue , microbiology and biotechnology , chemistry , biochemistry , gene , smooth muscle , genetics , botany
Vascular calcification increases the risk of cardiovascular mortality. We previously reported that expression of elastin decreases with progression of inorganic phosphorus (Pi)‐induced vascular smooth muscle cell ( VSMC ) calcification. However, the regulatory mechanisms of elastin mRNA expression during vascular calcification remain unclear. Micro RNA ‐29 family members (miR‐29a, b and c) are reported to mediate elastin mRNA expression. Therefore, we aimed to determine the effect of miR‐29 on elastin expression and Pi‐induced vascular calcification. Calcification of human VSMC s was induced by Pi and evaluated measuring calcium deposition. Pi stimulation promoted Ca deposition and suppressed elastin expression in VSMC s. Knockdown of elastin expression by sh RNA also promoted Pi‐induced VSMC calcification. Elastin pre‐ mRNA measurements indicated that Pi stimulation suppressed elastin expression without changing transcriptional activity. Conversely, Pi stimulation increased miR‐29a and miR‐29b expression. Inhibition of miR‐29 recovered elastin expression and suppressed calcification in Pi‐treated VSMC s. Furthermore, over‐expression of miR‐29b promoted Pi‐induced VSMC calcification. RT ‐ qPCR analysis showed knockdown of elastin expression in VSMC s induced expression of osteoblast‐related genes, similar to Pi stimulation, and recovery of elastin expression by miR‐29 inhibition reduced their expression. Our study shows that miR‐29‐mediated suppression of elastin expression in VSMC s plays a pivotal role in osteoblastic differentiation leading to vascular calcification.