[Regulation of alpha(1) type I collagen promoter by cytokines and losartan].
OBJECTIVE
To study the roles of transforming growth factor (TGF) beta(1), PDGF and losartan on regulation of collagen gene promoter.


METHODS
To rat mesangial cells transfected by pCOLH 1.5 and pCOLH 2.5, which were composed of different length of alpha(1) type I collagen gene promoter segments and chloramphenicol acetyltransferase (CAT) were added different concentrations of TGF beta(1), PDGF, Ang II and losartan. The activity of CAT was measured by ELISA technique.


RESULTS
TGF beta(1) enhanced the activity of pCOLH 1.5 and pCOLH 2.5 dose-dependently, showing significant difference with the control (P < 0.01). CAT activities of pCOLH 1.5 and pCOLH 2.5 were not affected with 10 micro g/L and 25 micro g/L of PDGF (P > 0.05). Ang II could increase the CAT activity of the two recombinants. Losartan inhibited the transcriptional activity of the promotor. Losartan + Ang II decreased the enhancement of the activity of promoter recombinant CAT (P < 0.01).


CONCLUSIONS
In mesangial cells, TGF beta(1) enhanced the activity of alpha(1) type I collagen promoter. PDGF did not significantly regulate the activity of CAT. Losartan prevented the increase of the activity of promoter transcription induced by Ang II partly.
Zhou
Chunhua
C
Department of Nephrology, Navy General Hospital, Beijing 100037, China.
Mei
Changlin
C
Gao
Chunfang
C
Lei
Xia
X
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D024042:Collagen Type I / Q000235:genetics* / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D016207:Cytokines / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D019808:Losartan / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D016207:Cytokines; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000804:Angiotensin II; D015500:Chloramphenicol O-Acetyltransferase; D019808:Losartan