Knockdown of LOXL1 inhibits TGF-beta 1-induced proliferation and fibrogenesis of hepatic stellate cells by inhibition of Smad2/3 phosphorylation

Liver fibrosis is pathological condition that seriously threatens human health. The lysyl oxidase (LOX) family has been reported to promote liver fibrosis. However, the effect of LOX-like 1 (LOXL1), a member of LOX family, on fibrogenesis of hepatic stellate cells (HSCs) remains unknown. The current study aimed to investigate the role of LOXL1 in liver fibrosis and the potential mechanism. We found that the mRNA and protein levels of LOXL1 were increased in transforming growth factor-beta 1 (TGF-beta 1)-stimulated human hepatic stellate cell line LX-2. Knockdown of LOXL1 inhibited the proliferation of TGF-beta 1-stimulated LX-2 cells. Knockdown of LOXL1 suppressed TGF-beta 1-induced expression of metalloproteinase type 1 (TIMP1), alpha-smooth muscle actin (alpha-SMA), and collagen type I (Col-I), as well as phosphorylation of Smad2 and Smad3 in LX-2 cells. In addition, the cell proliferation and fibrogenesis mediated by TGF-beta 1 stimulation and LOXL1 overexpression were abolished by knockdown of Smad2 and Smad3. Collectively, knockdown of LOXL1 suppressed cell proliferation and fibrogenesis in TGF-beta 1-stimulated HSCs via regulating the phosphorylation of Smad2/3.