RNF2 Mediates Hepatic Stellate Cells Activation by Regulating ERK/p38 Signaling Pathway in LX-2 Cells

The therapeutic approach of liver fibrosis is still an unsolved clinical problem worldwide. Notably, the accumulation of extracellular matrix (ECM) in the liver is mediated by the production of cytokines and growth factors, such as transforming growth factor-beta 1 (TGF-beta 1) in hepatic stellate cells (HSCs). Ring finger protein 2 (RNF2) was identified as the catalytic subunit of polycomb repressive complex 1 (PRC1), mediating the monoubiquitination of histone H2A. In recent years, a growing amount of evidence suggests that RNF2 may play an important role in multiple pathological processes involved in cancer. Here, we explored the role of RNF2 in liver fibrogenesis and its potential mechanisms. The results showed that RNF2 was up-regulated in human fibrotic liver tissue. Knockdown of RNF2 led to a decreasing expression of collagen1 and alpha-smooth muscle actin (alpha-SMA) in LX-2 cells, which was upregulated by RNF2 overexpression. Moreover, RNF2 overexpression significantly promoted TGF-beta 1-induced LX-2 cell proliferation but decreased apoptosis. Furthermore, knockdown of RNF2 inhibited the activation of ERK/p38 signaling pathways induced by TGF-beta 1. These data suggested that RNF2 is an effective pro-fibrogenic factor for HSC activation via ERK/p38 signaling pathway. RNF2 inhibition might be a promising therapeutic target for liver fibrosis.

Automated summary

The up-regulation of RNF2 in liver fibrosis enhances HSC activation and exerts fibrogenic effects by inhibiting the ERK/p38 signaling pathway induced by TGF-beta 1. The inhibition of RNF2 may be a promising therapeutic target for liver fibrosis.