Suppressive effect of SATB1 on hepatic stellate cell activation and liver fibrosis in rats

• SATB1 is downregulated in activated hepatic stellate cells.
• SATB1 inhibits the activation, proliferation, migration, and collagen production of hepatic stellate cells.
• SATB1 down-regulates CTGF expression through the Ras/Raf-1/MEK/ERK/Ets-1 pathway.
• SATB1 deactivates HSCs in vivo and attenuates liver fibrosis in rat.

Liver fibrosis is a worldwide clinical issue. Activation of hepatic stellate cells (HSCs) is the central event during liver fibrosis. We investigated the role of SATB1 in HSC activation and liver fibrogenesis. The results show that SATB1 expression is reduced during HSC activation. Additionally, SATB1 inhibits HSC activation, proliferation, migration, and collagen synthesis. Furthermore, CTGF, a pro-fibrotic agent, is also significantly inhibited by SATB1 through the Ras/Raf-1/MEK/ERK/Ets-1 pathway. In vivo, SATB1 deactivates HSCs and attenuates fibrosis in TAA-induced fibrotic rat livers. These data indicate that SATB1 plays an important role in HSC activation and liver fibrosis.