Effect of cyclosporine and sirolimus on the expression of connective tissue growth factor in rat experimental chronic nephrotoxicity

Fuad S. Shihab, William M. Bennett, Hong Yi, Takeshi F. Andoh

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Background/Aims: Connective tissue growth factor (CTGF) is a pro-fibrotic growth factor that acts downstream of transforming growth factor (TGF)-β. However, CTGF regulation remains unknown. We tried to determine the effect of two commonly used immunosuppressants, cyclosporine (CsA) and sirolimus (SRL), on CTGF expression in a model of chronic nephrotoxicity. Methods: Adult Sprague-Dawley rats kept on a low-salt diet were treated daily for 4 weeks with vehicle (VH), SRL (0.3 mg/kg), CsA5 (5 mg/kg), CsA10 (10 mg/kg) or both CsA5 and SRL. CTGF and TGF-β1 expressions were evaluated by Northern blot. Functional and histologic parameters in addition to number of apoptotic cells were determined. Results: At 28 days, both CsA doses were capable of inhibiting CTGF mRNA expression to levels similar to control. On the other hand, SRL increased CTGF expression by 3.5-fold. However, addition of CsA to SRL completely reversed that trend and returned levels to control. The results were different for TGF-β1, which was increased by both CsA and SRL and to a greater extent by the drug combination. Conclusion: Unlike TGF-β, CTGF does not seem to play an important role in CsA-induced chronic nephrotoxicity. In addition, calcineurin-dependent pathways are likely involved in CTGF regulation.

Original languageEnglish (US)
Pages (from-to)400-407
Number of pages8
JournalAmerican Journal of Nephrology
Volume26
Issue number4
DOIs
StatePublished - Sep 2006
Externally publishedYes

Keywords

  • Apoptosis
  • Connective tissue growth factor
  • Cyclosporine
  • Nephrotoxicity
  • Sirolimus

ASJC Scopus subject areas

  • Nephrology

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