[Effects of cyclosporin A combined with T4 on collagen IV production, coll alpha 1 (IV) mRNA and TGF beta 1 mRNA expression in cultured human mesangial cells].
OBJECTIVE
To investigate the effects of single cyclosporin A (CsA), tripcholorlide (T4) or both on renal fibrosis.


METHODS
Collagen IV concentrations in the supernatants of human mesangial cells (HMCs) in culture were measured by ELISA. Collagen type IV alpha 1 mRNA (Coll alpha 1 IV mRNA) and transforming growth factor beta 1 (TGF beta 1) mRNA expression were tested by RT-PCR.


RESULTS
CsA regulated HMC collagen IV production biphysically, i.e., 1.0 microgram/ml CsA increased collagen synthesis while 0.01-0.1 microgram/ml CsA decreased its formation. T4 enhanced collagen IV production in a dose dependent manner. Combination of the two drugs in lower doses could reach the same degree of immunosuppression as a higher dose of CsA did but with less fibrogenesis. Both CsA and T4 up-regulated HMC Coll alpha 1 (IV) mRNA and TGF beta 1 mRNA expression. The degree of Coll alpha 1 (IV) mRNA expression in different groups were in accordance with that of TGF beta 1 mRNA.


CONCLUSIONS
Both CsA and T4 regulate extracellular matrix formation which may be mediated by TGF beta 1. Combination of the two drugs in lower dose results in less fibrosis than a higher dose of CsA.
Su
Y
Y
Department of Nephrology, PUMC Hospital, CAMS and PUMC, Beijing 100730.
Li
X
X
Gao
Y
Y
Lin
J
J
Li
L
L
D002478:Cells, Cultured; D024141:Collagen Type IV / Q000096:biosynthesis* / Q000235:genetics; D016572:Cyclosporine / Q000494:pharmacology*; D004224:Diterpenes / Q000494:pharmacology*; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D010616:Phenanthrenes; D012333:RNA, Messenger / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D053773:Transforming Growth Factor beta1
D024141:Collagen Type IV; D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D010616:Phenanthrenes; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C068051:tripchlorolide; D016572:Cyclosporine