[Effects of rosiglitazone on the expression of connective tissue growth factor in the pulmonary arteries of rats suffering from fibrosis in lung].
OBJECTIVE
To explore the effects of rosiglitazone (RSG), an agonist of peroxisome proliferators-activated receptor-gamma (PPAR-gamma), on the up-regulation of connective tissue growth factor (CTGF) and the deposition of type I and type III collagens in the pulmonary arteries of rats suffering from fibrosis in lung.


METHODS
Forty-eight male Sprague-Dawley rats were randomly divided into 4 groups: bleomycin (BLM) plus normal saline (NS) group (n=21), BLM plus RSG group (n=9), NS plus NS group (n=9), and NS plus RSG group (n=9). The rats were received single intratracheal instillation of BLM (5 mg/kg bw) or equal volume of NS as control, and received intra-gastric adminnistration of RSG (3 mg/(kg x day), 14 day) or the same volume of NS as vehicle. In vio, the observation was conducted on day 14 after intratracheal instillation. In vitro, the pulmonary arteries of rats on day 14 after BLM were isolated and incubated with DMEM alone or with RSG (37 degrees C, 5% CO2, for 24 h.


RESULTS
In vivo, the expression and the content of CTGF, the contents of type I and type III collagens, and the ratio of type I collagen and type III collagen were increased in the pulmonary arteries of BLM-instilled rats, compared with those of NS-instilled rats (All P < 0.05). The above abnormal changes were ameliorated by RSG (All P < 0.05). In vitro, RSG blocked the up-regulation of CTGF (P < 0.05), but not the deposition of type I collagen and type III collagen in the pulmonary arteries isolated from the BLM-instilled rats (P > 0.05).


CONCLUSIONS
The results suggest that RSG directly blocks the up-regulation of CTGF in pulmonary arteries of rats suffering from fibrosis in lung, and this might be one of the mechanisms underling the ameliorated pulmonary arterial remodeling by RSG.
Cui
Mao-xiang
MX
Department of Pathophysiology, Institute of Basic Medical Science, Hebei Medical University, Shijiazhuang, China.
Chen
Xiao-ling
XL
Chen
Chao
C
Hu
Xiao-jie
XJ
Jin
Hui
H
D000818:Animals; D001761:Bleomycin; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D008168:Lung / Q000473:pathology; D008297:Male; D047495:PPAR gamma / Q000819:agonists; D011651:Pulmonary Artery / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
C526316:CCN2 protein, rat; D024042:Collagen Type I; D024061:Collagen Type III; D047495:PPAR gamma; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D001761:Bleomycin; D055513:Connective Tissue Growth Factor