Genetic or pharmacologic inhibition of EGFR ameliorates sepsis-induced AKI.

ABSTRACT: Despite recent studies have demonstrated that the EGF receptor (EGFR) activation provided a renoprotective role during ischemic and folic acid-induced AKI, the role and regulation mechanism of EGFR in septic AKI remains unclear. Here, gefitinib, a highly selective EGFR inhibitor, abrogated LPS-induced phosphorylation of EGFR, ERK1/2, and STAT3 as well as expression of COX, eNOS, and proinflammatory cytokines in HK-2 cells. In addition, c-Src is an upstream of EGFR signaling pathway and mediates LPS-induced EGFR transactivation. In vivo, either gefitinib or genetic approaches (Wave-2 mutant mice, which have reduced EGFR tyrosine kinase activity) protected against LPS or cecal ligation and puncture (CLP) induced AKI respectively. Interestingly, the beneficial effects of gefitinib or g

SUBMITTER: Xu X 

PROVIDER: S-EPMC5710948 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature