Kim Kwangho, Yang Dong Kwon, Kim Sunghwan, Kang Hara
Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon, 406-772, Republic of Korea.
Icahn School of Medicine at Mount Sinai, New York, NY.
J Cell Biochem. 2015 Oct;116(10):2325-33. doi: 10.1002/jcb.25183.
The transforming growth factor β (TGFβ) signaling pathway is critical for the promotion and maintenance of the contractile phenotype of vascular smooth muscle cells (VSMCs). Though multiple microRNAs (miRNAs) implicated in the regulation of the VSMC phenotype have been identified, the modulation of miRNAs in the VSMCs by TGFβ signaling has not been fully described. In this study, we identified microRNA-142-3p (miR-142-3p) as a modulator of the VSMC phenotype in response to TGFβ signaling. We show that miR-142-3p is induced upon TGFβ signaling, leading to the repression of a novel target, dedicator of cytokinesis 6 (DOCK6). The downregulation of DOCK6 by miR-142-3p is critical for cell migration. Thus, this study demonstrates that miR-142-3p is a key regulator of the TGFβ-mediated contractile phenotype of VSMCs that acts through inhibiting cell migration through targeting DOCK6.
转化生长因子β(TGFβ)信号通路对于促进和维持血管平滑肌细胞(VSMC)的收缩表型至关重要。尽管已经鉴定出多种参与调节VSMC表型的微小RNA(miRNA),但TGFβ信号对VSMC中miRNA的调节尚未得到充分描述。在本研究中,我们鉴定出微小RNA-142-3p(miR-142-3p)是响应TGFβ信号的VSMC表型调节剂。我们发现miR-142-3p在TGFβ信号作用下被诱导产生,导致一个新靶点——胞质分裂 dedicator 6(DOCK6)受到抑制。miR-142-3p对DOCK6的下调对于细胞迁移至关重要。因此,本研究表明miR-142-3p是TGFβ介导的VSMC收缩表型的关键调节因子,它通过靶向DOCK6抑制细胞迁移来发挥作用。