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MicroRNA‐21 represses human cystathionine gamma‐lyase expression by targeting at specificity protein‐1 in smooth muscle cells
Author(s) -
Yang Guangdong,
Pei Yanxi,
Cao Qiuhui,
Wang Rui
Publication year - 2012
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.24006
Subject(s) - downregulation and upregulation , microrna , cystathionine gamma lyase , vascular smooth muscle , cystathionine beta synthase , gene expression , microbiology and biotechnology , biology , phenotype , messenger rna , regulation of gene expression , gene , chemistry , enzyme , biochemistry , cysteine , endocrinology , smooth muscle
Cystathionine gamma‐lyase (CSE) is the major H 2 S‐generating enzyme in vascular smooth muscle cells (SMCs). CSE/H 2 S system contributes to the maintenance of SMC phenotype, and transcript factor specificity protein‐1 (SP1) is a critical regulator of CSE expression during SMC differentiation. The involvements of microRNA‐21 (miR‐21) in cardiovascular pathophysiology have been known, however miR‐21 regulation of CSE and SP1 as well as SMC phenotype are uncertain. Using quantitative real‐time PCR, we demonstrated that the expression of miR‐21 was upregulated in dedifferentiated human aorta SMCs (HASMCs) and injured mouse carotid arteries. To determine the potential roles of miR‐21 in SP1‐mediated CSE gene expression and SMC phenotypic change, we showed that miR‐21 expression was upregulated by miR‐21 precursor. Interestingly, miR‐21 overexpression significantly repressed the protein expressions of both CSE and SP1, inhibited H 2 S production, stimulated SMC proliferation, and reduced SMC differentiation marker gene expression, respectively. The mRNA expression of CSE but not SP1 was inhibited by miR‐21 precursor. Blockage of SP1 binding by mithramycin or inhibition of CSE activity by DL ‐propargylglycine did not change miR‐21 expression. We further demonstrated that miR‐21 repressed SP1 protein expression by directly targeting at SP1 3′ untranslational regions, which in turn downregulated CSE mRNA expression and stimulated SMC proliferation. Take together, these results suggest that miR‐21 participates in CSE/H 2 S‐mediated‐SMC differentiation by targeting SP1 . J. Cell. Physiol. 227: 3192–3200, 2012. © 2011 Wiley Periodicals, Inc.