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Mycophenolate Mofetil Ameliorates Arteriolopathy and Decreases Transforming Growth Factor‐β1 in Chronic Cyclosporine Nephrotoxicity
Author(s) -
Shihab Fuad S.,
Bennett William M.,
Yi Hong,
Choi Seung Ok,
Andoh Takeshi F.
Publication year - 2003
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1046/j.1600-6135.2003.00244.x
Subject(s) - medicine , mycophenolate , urology , nephrotoxicity , transplantation , toxicity
Afferent arteriolopathy is the most characteristic lesion of chronic cyclosporine (CsA) nephrotoxicity. We investigated the effect of therapeutic doses of mycophenolate mofetil (MMF) in a model of chronic CsA nephrotoxicity where transforming growth factor‐β (TGF‐β) was shown to play a central role . Rats treated with vehicle, MMF 10 mg/kg/day, CsA 10 mg/kg/day or CsA + MMF were sacrificed at 7 or 28 days. Physiologic and histologic changes were studied in addition to TGF‐β1 mRNA and protein expressions, and mRNA expression of plasminogen activator inhibitor‐1 (PAI‐1) and the extracellular matrix (ECM) proteins biglycan and types I and IV collagen . While MMF markedly ameliorated afferent arteriolopathy, it had no significant effect on interstitial fibrosis and tubular atrophy. In addition, MMF treatment reduced both TGF‐β1 mRNA and protein levels by 39% and 32%, respectively (p < 0.05 vs. CsA only). The expression of the ECM proteins followed that of TGF‐β1 and was significantly decreased with MMF; a similar effect was observed with PAI‐1, suggesting an increase in ECM degradation . These results suggest that MMF exerts a beneficial effect on CsA arteriolopathy and that it decreases TGF‐β1. While this drug combination may be useful clinically, long‐term studies are needed to determine if MMF has a lasting benefit .