Expression and significance of Sirt1 in renal allografts at the early stage of chronic renal allograft dysfunction

Abstract

Objective: To investigate the expression and significance of Sirt1 in renal allografts at the early stage of chronic renal allograft dysfunction (CRAD).

Methods: CRAD rat models were established using classical orthotopic F344-Lewis kidney transplantation. F344 and Lewis uninephrectomized rats were used as controls. Twelve weeks after the operation, the rats were sacrificed for renal function, histological, immunohistochemistry and molecular biological analyses.

Results: The 24-h urinary protein excretion and serum creatinine levels, urine microalbumin/creatinine ratios, and Banff score sums were significantly increased in the CRAD group compared with those in the F344 and Lewis control groups. The degree of mononuclear cell infiltration and interstitial fibrosis (IF) was higher in the CRAD group than in the control groups. Sirt1, TGF-β1, MCP-1, ICAM-1 expression was up-regulated in CRAD. Furthermore, Sirt1 expression was negatively correlated with the 24-h urinary protein excretion and serum creatinine levels, Banff score sums, mononuclear cell infiltration and IF severity, and TGF-β1, MCP-1 and ICAM-1 expression levels.

Conclusion: Sirt1 might be involved in the pathogenic process of IF and inflammation at the early stage of CRAD. Thus, Sirt1 represents a novel therapeutic strategy and target for the early prevention and treatment of CRAD.

Keywords: Chronic renal allograft dysfunction; Inflammation; Interstitial fibrosis; Sirt1.