A team of researchers, led by Professor SHEN Xu, at Shanghai Institute of Materia Medica, Chinese Academy of Science, found that activation of protein serine/threonine phosphatase PP2Cα efficiently prevents liver fibrosis. This study was cooperated with HU Lihong group and carried out by WANG Lirui, WANG Xu, et al.
Liver fibrosis is a major public health threat causing portal hypertension, liver failure, and risk of hepatocellular carcinoma. Hepatic stellate cells (HSCs) play critical roles in liver fibrogenesis. Once intoxicated by stimuli, quiescent HSCs could transdifferentiate into activated HSCs which secrete some proinflammatory and profibrogenic cytokines such as tumor necrosis factor alpha (TNFa) and transforming growth factor beta (TGFb), leading to over-accumulation of extracellular matrix (ECM) and altered matrix degradation. Meanwhile, these cytokines further activate HSCs and enhance their proliferation and survival, thus exacerbating fibrogenesis. The authors found thatactivation of protein serine/threonine phosphatase PP2Caby overexpression or the new discovered small molecular activator NPLC0393 terminated TGFb-Smad3 and TGFb-p38 signaling pathways, induced cell cycle arrest in HSCs and decreased a-smooth muscle actin (a-SMA) expression, collagen deposition and hepatic hydroxyproline (HYP) level in CCl4- and BDL-induced mice. This study suggested that PP2Ca activation might be an attractive new strategy for treating liver fibrosis while the small molecular activator NPLC0393 might represent a lead compound for antifibrogenic drug development. The researchers have applied for patent about this finding.
This research entitled "Activation of Protein Serine/Threonine Phosphatase PP2Cα Efficiently Prevents Liver Fibrosis" was published in Plos One on Dec 6, 2010.