CTGF regulates cyclic stretch-induced vascular smooth muscle cell proliferation via microRNA-19b-3p
CTGF regulates cyclic stretch-induced vascular smooth muscle cell proliferation via microRNA-19b-3p
复制标题
CTGF 通过 microRNA-19b-3p 调节循环拉伸诱导的血管平滑肌细胞增殖
DOI：
10.1016/j.yexcr.2019.01.015
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发表时间：
2019-03-01
影响因子：
3.7
通讯作者：
Han, Yue
中科院分区：
文献类型：
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作者：
Wang, Wen-Bin;Li, Hai-Peng;Han, Yue
周期性牵张对高血压血管重构过程中血管平滑肌细胞增殖的调节作用，但其机制尚待进一步研究。结缔组织生长因子（CTGF）与细胞增殖、迁移、粘附等多种细胞功能密切相关。在此，CTGF在VSMC中的作用被研究在响应机械循环拉伸。在这里，我们表明，CTGF是上调在体内和体外高血压期间。CTGF过表达显著促进VSMC增殖，而CTGF敲低则减弱周期性牵张诱导的增殖。此外，3 'UTR报告基因分析显示microRNA-19 b-3 p（miR-19 b-3 p）直接调控CTGF表达。在病理条件下（如15%周期性牵张），miR-19 b-3 p表达显著下调;相反，miR-19 b-3 p过表达阻断VSMC增殖。综上所述，这些发现表明，病理性周期性牵张通过促进VSMC增殖经由miR-19 b-3 p/CTGF通路诱导血管重塑，并指出CTGF作为高血压的潜在治疗靶点。
Cyclic stretch regulates proliferation of vascular smooth muscle cells (VSMCs) during hypertension-induced vascular remodeling, but the underlying mechanisms remain to be studied. Connective tissue growth factor (CTGF) has been reported associated with several cellular function such as proliferation, migration and adhesion. Herein, the role of CTGF in VSMCs was investigated in response to mechanical cyclic stretch. Here we show that CTGF is up-regulated both in vivo and in vitro during hypertension. Overexpression of CTGF markedly promoted VSMC proliferation, whereas CTGF knockdown attenuated cyclic stretch-induced proliferation. Furthermore, 3'UTR reporter assays revealed that microRNA-19b-3p (miR-19b-3p) directly regulates CTGF expression. Under pathological condition (e.g. 15% cyclic stretch), miR-19b-3p expression was significantly down-regulated; conversely miR-19b-3p overexpression blocked VSMC proliferation. Taken together, these findings indicate that pathological cyclic stretch induces vascular remodeling by promoting VSMC proliferation via miR-19b-3p/CTGF pathway, and point to CTGF as a potential therapeutic target for hypertension.