title: The antihepatic fibrotic effects of fluorofenidone via MAPK signalling pathways.
abstract: BACKGROUND
  Fluorofenidone (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).
  
  
  METHODS
  Wistar 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.
  
  
  RESULTS
  AKF-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.
  
  
  CONCLUSIONS
  AKF-PD treatment inhibits the progression of hepatic fibrosis by suppressing HSCs proliferation and activation via MAPK signalling pathway.
authors: Department of Nephropathy, Xiangya Hospital, Central South University, Changsha, China.
authors: Yu
authors: Y
authors: Peng
authors: Huixiang
authors: H
authors: Yang
authors: Tingting
authors: T
authors: Zhu
authors: Menghua
authors: M
authors: Zhao
authors: Yuexia
authors: Y
authors: Deng
authors: Bin
authors: B
authors: Liu
authors: Hong
authors: H
authors: Shen
authors: Gaoyun
authors: G
authors: Hu
authors: Zhaohe
authors: Z
authors: Wang
authors: Lijian
authors: L
authors: Tao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D004128:Dimethylnitrosamine / Q000633:toxicity; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000201:enzymology; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000502:physiology*; D008297:Male; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics; D023421:Models, Animal; D011728:Pyridones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics
chemical_list: C511655:5-methyl-1-(3-fluorophenyl)-2-(1H)-pyridone; D011728:Pyridones; D012333:RNA, Messenger; C576839:TIMP1 protein, rat; D019715:Tissue Inhibitor of Metalloproteinase-1; D048031:JNK Mitogen-Activated Protein Kinases; D048055:Mitogen-Activated Protein Kinase 8; D048051:p38 Mitogen-Activated Protein Kinases; D004128:Dimethylnitrosamine