Role of transforming growth factor-β1 in experimental chronic cyclosporine nephropathy

Fuad S. Shihab, Takeshi F. Andoh, Amie M. Tanner, Nancy A. Noble, Wayne A. Border, Nora Franceschini, William M. Bennett

Research output: Contribution to journalArticlepeer-review

215 Scopus citations


The pathogenesis of fibrosis in chronic cyclosporine (CsA) nephropathy remains unknown. Since TGF-β1 plays a key role in the fibrogenesis of a number of renal diseases, we studied a salt-depleted rat model of chronic CsA nephropathy which shows similarity to the structural and functional lesions described in patients. Pair fed rats were treated with either CsA (15 mg/kg/day s.c.) or an equivalent dose of olive oil and sacrificed at 7 and 28 days. Characteristic histologic changes of proximal tubular injury, tubulointerstitial fibrosis and arteriolopathy developed in CsA-treated rats at day 28. They were accompanied by physiologic changes of increased serum creatinine, decreased creatinine clearance, increased enzymuria and decreased concentrating ability. CsA-treated rats showed a progressive increase in mRNA expression of TGF-β1 and matrix proteins at days 7 and 28. Most of the changes were in the tubulointerstitial and vascular compartments by immunofluorescence with a predominant involvement of the medulla as compared to cortex. The mRNA expression of plasminogen activator inhibitor, a protease inhibitor stimulated by TGF-β1, followed TGF-β1 and matrix proteins, suggesting that the fibrosis of chronic CsA nephropathy likely involves the duel action of TGF-β on matrix deposition and degradation.

Original languageEnglish (US)
Pages (from-to)1141-1151
Number of pages11
JournalKidney International
Issue number4
StatePublished - 1996
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology


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