Caspase-7, Fas and FasL in long-term renal ischaemia/reperfusion and immunosuppressive injuries in rats.
OBJECTIVE
Ischaemia/reperfusion (I/R) injury is important in kidney transplantation. We have previously demonstrated that long-term I/R injury and immunosuppression affect apoptosis and inflammation, but the underlying mechanisms are far from clear. In this study, the involvement of caspase-7, Fas and FasL was further investigated.


METHODS
The right renal pedicle was clamped for 45 min followed by left nephrectomy in 40 rats. Cyclosporine (CsA), tacrolimus (Tac), rapamycin (Rap) or mycophenolate mofetil (MMF) were administered daily for 16 weeks. Caspase-7, Fas and FasL expression, and their correlations with caspase-3, apoptosis, inflammation, renal structure and function were evaluated.


RESULTS
Active caspase-7 was significantly increased in I/R and CsA-treated kidneys and decreased by Tac, Rap and MMF, while the caspase-7 precursor was enhanced by Rap. Active caspase-7-stained cells were scattered throughout the tubulointerstitium and often had apoptotic features. Fas, but not FasL, was increased in I/R and CsA-treated kidneys and decreased by Rap and MMF. Fas and FasL proteins were mainly located in dilated tubules. There were close correlations among caspase-7, Fas, caspase-3, apoptosis, inflammation, renal structure and function.


CONCLUSIONS
Caspase-7, associated with caspase-3, apoptosis and inflammation, might be involved in long-term I/R and immunosuppressive injury, at least in part through the Fas-signalling pathway.
Yang
Bin
B
Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK. by5@le.ac.uk
Harris
Kevin P G
KP
Jain
Sunjay
S
Nicholson
Michael L
ML
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism*; D053222:Fas Ligand Protein / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D009393:Nephritis / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology; D019014:fas Receptor / Q000378:metabolism*
D053222:Fas Ligand Protein; D007166:Immunosuppressive Agents; D019014:fas Receptor; D053148:Caspase 3; D053179:Caspase 7