Role And Mechanism Of Caspase-1Mediated PARP1Activation In Tubulointerstitial Fibrosis

Objectives To investigate the role and mechanism of caspase-1and PARP1in renal interstitial fibrosis.Methods UUO was performed in wild-type and caspase-1-knock out C57BL/6J mice. Then mice were divided into4groups, WT sham-operated, WT UUO, KO sham-operated and KO UUO. After7days, the mice were sacrificed and the renal tissues were prepared for western blot analysis and RT-PCR to detect the protein and mRNA levels of activated caspase-7, as well as PARP1and α-SMA. Also immunohistochemistry was used to display the distribution and levels of α-SMA and fibronectin. The masson trichrome staining showed the collagen distribution and levels.Results Caspase-7was dramatically activated in the wild-type UUO groups. When compared with wild-type UUO group, the caspase-1knock-out group showed decreased level of activated caspase-7(P<0.05), so was the protein and mRNA levels of a-SMA (P<0.05). However, the cleavage and activation of PARP1was not changed between wild-type UUO and knock-out UUO groups. It was observed that the a-SMA expression was markedly increased in the wild-type UUO group in comparison to sham-operated group by immunohistochemistry, while the α-SMA protein level was down regulated in the knock-out UUO group((P<0.05). Consistent with the immunohistochemistry, the masson trichrome staining showed a decrease in collagen levels in knock-out UUO group.Conclusions Caspase-1gene knock-out could inhibit the activation of caspase-7, also downregulate the expression of α-SMA and fibronectin, thus attenuate the renal interstitial fibrosis. This suggest caspase-1-caspase-7signaling may play an important role in renal interstitial fibrosis.