Fluorofenidone inhibits TGF-beta1 induced CTGF via MAPK pathways in mouse mesangial cells.
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.
Wang
Ling
L
Division of Nephropathy, Department of Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Hu
Gao-yun
GY
Shen
Hong
H
Peng
Zhang-zhe
ZZ
Ning
Wang-bin
WB
Tao
Li-jian
LJ
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*
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