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

Abstract

Background: Acute 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 antiapoptotic 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.Methods: Wild-type C57 mice and adiponectin-knockout (KO) mice were divided into 6 groups: the wildtype 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.Results: Compared 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.Conclusions: Through 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.

Szechwan Lovage Rhizome Extract Improves Renal Function and Alleviates Inflammatory Responses in Pyelonephritis Rats Infected with Escherichia Coli via IL-6/STAT3 Axis

“…As we all know, the IL-6/STAT3 axis is one of the classic pro-inflammatory pathways, which has been proven to be critical in regulating IRs in many diseases (14,25). In APN, significant abnormal activation of IL-6/STAT3 has also been confirmed (26). In this study, the IL-6, STAT3 and their phosphorylated proteins were increased in the model group, confirming the activation of this axis in APN.…”

Role of adiponectin in osteoarthritis

“…A recent study shows that adiponectin agonist ADP355 activates the Nrf2 and sirtuin 2 downstream pathways, thus reducing myocardial apoptosis and oxidative stress ( Zhao et al, 2020 ). In an acute pyelonephritis mouse model, exogenously administered adiponectin not only elevated adiponectin concentration and lipid content but also had antioxidant effects to reduce arterial stiffness and alleviate renal cell apoptosis and inflammation ( Afzal et al, 2021 ; Dai and He, 2021 ). Moreover, adiponectin suppressed oxidative/nitrative stress in the arterial endothelium of hyperlipidemic rats ( Li et al, 2007 ).…”