MiR-15b and miR-16 suppress TGF-β1-induced proliferation and fibrogenesis by regulating LOXL1 in hepatic stellate cells

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. • MiR-15b and miR-16 were down-regulated in TGF-β1-induced LX-2 cells. • MiR-15b and miR-16 suppresses the proliferation of activated LX-2 cells. • MiR-15b and miR-16 represses TGF-β1-induced fibrogenic response and activation of Smad2/3. • LOXL1 was a target of miR-15b and miR-16.