Adiponectin alleviated renal cell apoptosis and inflammation via inactivation of JAK2/STAT3 signal pathway in an acute pyelonephritis mouse model.

Abstract

BackgroundAcute pyelonephritis (APN), an acute and severe kidney infection, is usually treated with antibiotics. However, APN treatment has become increasingly challenging because of bacterial resistance. Adiponectin, an adipokine, has recently been reported to exhibit profound anti-inflammatory and anti-apoptotic effects. However, the effect of adiponectin on the outcomes of APN treatment remains unclear. In this study, we aimed to investigate the effects of adiponectin on APN and the mechanisms underlying these effects.MethodsWild-type C57 mice and adiponectin-knockout (KO) mice were divided into 6 groups: the wild-type control group, the wild-type model group, the wild-type adiponectin intervention group, the KO control group, the KO model group, and the adiponectin-KO intervention group. We measured white blood cell (WBC) and neutrophil counts (NC) using a multispecies hematology analyzer; tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) using enzyme-linked immunosorbent assay (ELISA); blood urea nitrogen (BUN) and serum creatinine (SCr) levels using colorimetry; and the protein levels of JAK2, STAT3, p-JAK2, p-STAT3, Bcl-2, and Bax in renal tissues using western blot analysis. Apoptotic cells were detected using the transferase-mediated dUTP nick end labelling (TUNEL) assay.ResultsCompared to the wild-type mice, the KO mice showed a more severe inflammatory response and kidney damage after Escherichia coli infection. After treatment with exogenous adiponectin injection, the inflammatory response, oxidative stress, and kidney damage were partly alleviated. Adiponectin KO led to JAK2/STAT3 signaling activation, and exogenous adiponectin administration inactivated JAK2/STAT3 signaling in the APN model. APN can lead to an increase in the level of the protein Bax and a decrease in the level of the bcl-2 protein, thereby increasing apoptosis; this effect was inhibited by adiponectin.ConclusionsThrough use of a pyelonephritis mouse model, we demonstrated that adiponectin might alleviate renal cell apoptosis and inflammatory response by inactivating the JAK2/STAT3 signaling pathway.