Department of Infectious Diseases, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou 450003, China.
Department of Infectious Diseases, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou 450003, China.
Life Sci. 2021 Apr 1;270:119144. doi: 10.1016/j.lfs.2021.119144. Epub 2021 Feb 2.
Activation of hepatic stellate cells (HSCs) is an important event during the progress of liver fibrosis. MicroRNA (miR)-15b and miR-16 have been found to be involved in activation of HSCs. However, the roles of miR-15b/16 in liver fibrosis remain unclear. The expression of miR-15b/16 was decreased in TGF-β1-stimulated LX-2 cells. Overexpression of miR-15b/16 in LX-2 cells suppressed TGF-β1-induced cell proliferation and the expression levels of tissue inhibitor of metalloproteinase type 1, collagen type I, and α-smooth muscle actin. The activation of Smad2/3 caused by TGF-β1 was repressed by miR-15b/16 overexpression. The two miRNAs directly bound to the 3'-UTR of lysyl oxidase-like 1 (LOXL1) and suppressed the LOXL1 expression. Furthermore, knockdown of LOXL1 attenuated miR-15b/16 downregulation-induced cell proliferation, fibrogenic response and phosphorylation of Smad2/3. Collectively, miR-15b/16 exhibited anti-fibrotic activity through regulation of Smad2/3 pathway.
肝星状细胞（HSCs）的激活是肝纤维化进展过程中的一个重要事件。已经发现 microRNA（miR）-15b 和 miR-16 参与了 HSCs 的激活。然而，miR-15b/16 在肝纤维化中的作用尚不清楚。在 TGF-β1 刺激的 LX-2 细胞中，miR-15b/16 的表达降低。在 LX-2 细胞中过表达 miR-15b/16 抑制了 TGF-β1 诱导的细胞增殖和组织金属蛋白酶抑制剂 1、I 型胶原和α-平滑肌肌动蛋白的表达水平。miR-15b/16 的过表达抑制了 TGF-β1 引起的 Smad2/3 的激活。这两种 miRNA 直接与赖氨酰氧化酶样 1（LOXL1）的 3'-UTR 结合，抑制 LOXL1 的表达。此外，LOXL1 的敲低减弱了 miR-15b/16 下调诱导的细胞增殖、纤维生成反应和 Smad2/3 的磷酸化。总之，miR-15b/16 通过调节 Smad2/3 通路表现出抗纤维化活性。
