Original Article Blockage of JAK/STAT signalling attenuates renal ischaemia-reperfusion injury in rats

Background. JAK/STAT signalling is one of the major pathways for cytokine signal transduction. However, the role of JAK/STAT in renal ischaemia/reperfusion (I/R) injury is not clear. The present study investigated the protection against renal I/R injury by in vivo inhibition of JAK2 activation. Methods. Rats subjected to renal I/R were either treated with daily intraperitoneal injection of selective JAK2 inhibitor tyrphostin AG490 (10mg/kg) or vehicle alone starting 4 h before, immediately after or until 3 h after I/R. Renal function, histology, infil-tration of macrophages, apoptosis, expression of chemokines and adhesion molecules were assessed. Results. AG490 treatment significantly inhibited the phosphorylation of JAK2 and its downstream mole-cule STAT1 and STAT3. Rats pretreated with AG490 exhibited improved renal function, attenuated histolo-gical lesions and reduced apoptosis of tubular epithe-lial cells. AG490 significantly inhibited renal expression of MCP-1 and ICAM-1 mRNA, as well as the expression of ICAM-1 protein, accompanied by decreased macrophage accumulation in the kidney. Immediate post-ischaemic treatment of AG490 also significantly ameliorated renal injury. However, delayed post-ischaemic treatment until 3 h after I/R failed to attenuate renal damage. Conclusions. This study demonstrated the involvement of JAK/STAT signalling in the pathogenesis of renal I/R injury, suggesting that JAK/STAT pathway may serve as a potential target for early intervention in ischaemic acute renal failure