Abstract
Sepsis-induced inflammatory damage and adaptive repair are critical in the pathophysiological mechanisms of acute kidney injury (AKI). Here, we investigated the role of interferon regulatory factor three (IRF3) and subsequent activation of the Hippo pathway in inflammatory damage and repair using an in vitro cell model of LPS-induced AKI. LPS caused the phosphorylation and activation of IRF3 in the early stages of sepsis, and activated IRF3 enhanced the production of type I interferon (IFN), resulting in an excessive inflammatory response. Furthermore, LPS generated considerably more inflammatory injury than intended cell death, and IRF3 activation triggered the Hippo pathway, causing a reduction in YAP, which eventually impaired proliferation and repair in surviving renal tubular epithelial cells and exacerbated the development of AKI. In conclusion, IRF3 promoted the development of sepsis-associated AKI (SAKI) by modulating the Hippo pathway.