• Yu Peng, Huixiang Yang, Tingting Zhu, Menghua Zhao, Yuexia Deng, Bin Liu, Hong Shen, Gaoyun Hu, Zhaohe Wang, and Lijian Tao.
• Department of Nephropathy, Xiangya Hospital, Central South University, Changsha, China.
• Eur. J. Clin. Invest. 2013 Apr 1;43(4):358-68.

BackgroundFluorofenidone (AKF-PD) is a novel pyridone agent. The purpose of this study is to investigate the inhibitory effects of AKF-PD on dimethylnitrosamine (DMN)-induced liver fibrosis in rats and the involved molecular mechanism related to hepatic stellate cells (HSCs).Materials And MethodsWistar rats were randomly divided into normal control, DMN, DMN/AKF-PD treatment and DMN/pirfenidone (PFD) treatment groups. AKF-PD and PFD treatments were, respectively, performed for two activated HSCs lines, rat CFSC-2G and human LX2. The cell proliferation was analysed by MTT. The expression of collagen I was determined by immunohistochemical staining and real-time RT-PCR. The expression of α-smooth muscle actin (α-SMA), tissue inhibitor of metalloproteinases-1 (TIMP-1), extracellular signal regulated kinase (ERK1/2), p38 MAPK (p38), and c-Jun N-terminal kinase/stress-activated protein kinase (JNK) were also detected by real-time RT-PCR and/or Western blot.ResultsAKF-PD significantly reduced PDGF-BB-induced proliferation and activation of HSCs, as determined by reducing protein expression of α-SMA and TIMP-1. AKF-PD treatment attenuated PDGF-BB-induced upregulation of phosphorylation of ERK1/2, p38 and JNK. In fibrotic rat liver, AKF-PD reduced the degree of liver injury and hepatic fibrosis, which was associated with reduced the expression of collagen I, α-SMA, TIMP-1 at both mRNA and protein levels.ConclusionAKF-PD treatment inhibits the progression of hepatic fibrosis by suppressing HSCs proliferation and activation via MAPK signalling pathway.© 2013 The Authors. European Journal of Clinical Investigation © 2013 Stichting European Society for Clinical Investigation Journal Foundation.

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