Influence of autophagy on acute kidney injury in a murine cecal ligation and puncture sepsis model

Abstract

The role of autophagy in the maintenance of renal homeostasis during sepsis is not well understood. We therefore aimed to determine the influence of autophagy on kidney during sepsis using a murine sepsis model, i.e. cecal ligation and puncture (CLP). In CLP treated animals, the number of autolysosomes observed by electron microscopy increased over time. The number of autophagosomes in CLP animals decreased relative sham operated controls at 24 hrs after CLP, indicating that autophagy flux is already diminishing by that time. Moreover, CLP induced an increase in LC3-II/LC3-I ratio at 6–8 hrs, demonstrated in western blots, as well as an increase in GFP-LC3 dots at 6–8 hrs and 24 hrs, using immunofluorescence and anti-LC3 and LAMP1 antibodies on tissue sections from GFP-LC3 transgenic mice. LC3-II/LC3-I ratio and the number of co-localized GFP-LC3 dots and LAMP1 signals (GFP LC3 + LAMP1 dots) in CLP mice at 24 hrs were significantly reduced compared with data obtained at 6–8 hrs. Notably, acceleration of autophagy by rapamycin resulted in improvement of renal function that was associated with improvement in the histologic severity of tubular epithelial injury in CLP treated animals. Autophagy in the kidney was significantly slowed in the kidney during the acute phase of sepsis; nonetheless, autophagy in kidney appears to play a protective role against sepsis.

PPARαcontributes to protection against metabolic and inflammatory derangements associated with acute kidney injury in experimental sepsis

“…Sunahara et al. () recently showed that WT C57/B6 mice subjected to CLP‐induced sepsis had increased autophagy in renal tubular epithelial cells 6–8 h after surgery, that decreased toward sham‐operated levels at 24 h. Our WT mice had only a mild elevation in the qualitative abundance in autophagosomes at 24 h, which could be consistent with Sunahara et al., but we did not evaluate our animals at the 6–8 h time point. Autophagy has been shown to be augmented in the liver by PPAR α signaling (Jiao et al.…”

Long noncoding RNA HOXA‐AS2 mediates microRNA‐106b‐5p to repress sepsis‐engendered acute kidney injury

“…These laboratorial mice were split into two groups, covering the Sham group and the cecal ligation and puncture (CLP) group. The CLP model was established in consonance with the description by Sunahara et al [ 16 ] The mice in the Sham group were managed with the same procedures but without ligation and puncture. The animal experiments were approved by the Laboratory Animal Management Committee of Jining No.1 People's Hospital.…”

Role of C‐reactive protein in the pathogenesis of acute kidney injury

“…22 Newer insights show that autophagy induction in response to multiple stresses for the induction of AKI is protective. 24,25 Therefore, autophagy is a potential therapeutic target and associated with the prognosis of AKI. Impaired autophagy negatively impacts AKI.…”