title: Fluorofenidone inhibits TGF-beta1 induced CTGF via MAPK pathways in mouse mesangial cells.
abstract: OBJECTIVE
  The development of novel antifibrotic agent candidates for the treatment of diabetic nephropathy. The present study was designed to investigate the potential mechanism of fluorofenidone involving the downregulation of CTGF expression induced by TGF-beta1 and the related signaling pathway in mouse mesangial cells (MMCs).
  
  
  METHODS
  Mouse mesangial cells were applied to explore the involvement of MAPK in TGF-beta1 signal pathway to CTGF, and the regulation of fluorofenidone. The activation of three major members of MAPK, including ERK1/2, P38 and JNK was detected by Western blot; the expression of CTGF was investigated by real time PCR and Western blot.
  
  
  RESULTS
  Fluorofenidone significantly reduced the phosphorylation of ERK1/2, P38 and JNK induced by TGF-beta1. Fluorofenidone, PD98059 and SB203580 could partially inhibit TGF-beta1-induced expression of CTGF in mouse mesangial cells, however, JNK inhibitor II had no effect.
  
  
  CONCLUSIONS
  The antifibrotic effects of fluorofenidone are suggested to be mediated byits actions through inhibition of MAPK activation and consequent reduction of CTGF expression.
authors: Division of Nephropathy, Department of Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Ling
authors: L
authors: Wang
authors: Gao-yun
authors: GY
authors: Hu
authors: Hong
authors: H
authors: Shen
authors: Zhang-zhe
authors: ZZ
authors: Peng
authors: Wang-bin
authors: WB
authors: Ning
authors: Li-jian
authors: LJ
authors: Tao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis* / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D011728:Pyridones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
chemical_list: C511655:5-methyl-1-(3-fluorophenyl)-2-(1H)-pyridone; C526318:CCN2 protein, mouse; D005343:Fibrinolytic Agents; D011728:Pyridones; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; D020928:Mitogen-Activated Protein Kinases