[The effect or rosiglitazone on signal pathways of transforming growth factor-beta1 in human lung fibroblast].
OBJECTIVE
To investigate the expression of CTGF, CTGF mRNA, NF-kappaB and AP-1 induced by TGF-beta1 in human lung fibroblast (HLF-02), and study the effect and possible mechanism of rosiglitazone on signal pathways of TGF-beta1 in HLF-02.


METHODS
The effects of TGF-beta1, curcumin, PDTC and rosiglitazone on the expression of CTGF, NF-kappaB and AP-1 were evaluated with Western blot. The expression of CTGF was also detected with immunohistochemistry assay. The level of CTGF mRNA was detected with RT-PCR.


RESULTS
(1) The CTGF protein levels of HLF-02 cells were significantly up-regulated after incubated with 1 ng/mL TGF-beta1 for 15 min (P<0.01 vs Control). The CTGF mRNA was also up-regulated. The levels of CTGF protein and CTGF mRNA expression was up-regulated by TGF-beta1 in a time-dependent manner. (2) The expression of NF-kappaB and AP-1 increased after HLF-02 cells were incubated with 1 ng/mL TGF-beta1 for 30 min (P<0.01 vs Control). The CTGF protein levels were inhibited obviously after HLF-02 cells were incubated with PDTC or curcumin. (3) The expression of CTGF, NF-kappaB and AP-1 decreased after pre-incubation with different doses of rosiglitazone (P<0.01 vs TGF-beta1 group). The CTGF mRNA were also markedly inhibited (P<0.01 vs TGF-beta1 group).


CONCLUSIONS
It is supposed that rosiglitazone inhibits CTGF expression induced by TGF-beta1 in HLF-02 cells by activating PPARgamma through NF-kappaB and AP-1 signal transduction pathways.
Shi
Jun-Qing
JQ
Department of Respiratory, West China Hospital, Sichuan University, Chengdu 610041, China.
Xie
Min
M
Wang
You-Juan
YJ
Ling
Wei
W
Wang
Hao-Ling
HL
D002460:Cell Line; D055513:Connective Tissue Growth Factor / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000166:cytology; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000077154:Rosiglitazone; D015398:Signal Transduction; D045162:Thiazolidinediones / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000502:physiology*
C526317:CCN2 protein, human; D016328:NF-kappa B; D012333:RNA, Messenger; D045162:Thiazolidinediones; D018808:Transcription Factor AP-1; D053773:Transforming Growth Factor beta1; D000077154:Rosiglitazone; D055513:Connective Tissue Growth Factor