| Background Liver fibrosis is a pathological process arising from continuous wound-healing responses to liver injury, which encompasses infection-related hepatic fibrosis, metabolic-type fibrosis, and biliary-type fibrosis. As the injury proceeds, the extracellular matrix(ECM) such as collagen and fibronectin accumulates and forms a fibrous scar to nodules of regenerating hepatocytes, which predisposes to liver failure and hepatocellular carcinoma. Protein tyrosine phosphatase receptor type O(PTPRO) is an important member of the receptor-type Protein-tyrosine phosphatases(PTPs), which is a key part of post-translational modification strategies to regulate protein activities. Previous research from our center has indicated that PTPRO expression promoted the sex difference in incidence of hepatocellular carcinoma. Furthermore, we also reported that PTPRO played a bidirectional role in hepatic ischemia/reperfusion(I/R). However, the role of PTPRO in liver fibrosis is still unclear.Methods: 1) We collected cirrhotic and normal liver tissue for real-time PCR for clinical verification to found the PTPRO level in patient samples. 2) To determine whether PTPRO played a critical role in liver fibrogenesis in vivo, we induced two different experimental fibrogenesis models by BDL and CCl4 administration in wild-type(WT) mice. 3) To test the functional importance of PTPRO in hepatic fibrosis, paired PTPRO KO mice and littermate WT mice were used in two kinds of models as mentioned above. 4) To establish the critical role of PTPRO in activated HSCs or hepatocellular, sh RNA specific for mouse PTPRO(PTPRO-sh RNA) was used to knockdown PTPRO expression with nonlethal concentrations of PDGF-BB.Results: In our current study, we demonstrated that PTPRO expression was reduced in mouse and human fibrotic liver tissue, and that PTPRO KO or knock-down plays a critical role in emolliating collagen deposition and HSC activation via PDGF/AKT and ERK pathways.Conclusion: PTPRO as a key mediator of hepatic fibrosis, and further explored the idea of therapeutic modulation of PTPRO in hepatic inflammation and fibrosis. |
