Abstract: PO0165
Augmenter of Liver Regeneration Protects Kidney from Ischemia-Reperfusion Injury via Regulation of TLR4/MAPKs Signaling Pathway
Session Information
- AKI Mechanisms - 1
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 101 AKI: Epidemiology, Risk Factors, and Prevention
Authors
- Li, Ying, ChongqingTraditional Chinese Medicine Hospital, Chongqing, China
- Xiong, Weijian, ChongqingTraditional Chinese Medicine Hospital, Chongqing, China
Background
Toll-like receptor 4 (TLR4) expressed within the ischemic kidney is a crucial mediator of innate activation and inflammation. The augmenter of liver regeneration (ALR) is an immunoregulator which is highly expressed in kidney upon induction of renal I/R injury. It has been shown that exogenous ALR can protect kidney against I/R injury. However, whether ALR’s protective effect results from its immune regulatory function has yet to be determined. In this study, we show that treating renal I/R induced-rats with recombinant human ALR (rhALR) protects them from kidney I/R.
Methods
Rats were randomized into 4 groups as follows: sham-operated group; I/R group; I/R+rhALR1 group; I/R+rhALR2 group. TLR4, neutrophils and macrophages were detected by immunochemistry. ERK, JNK, and p38 proteins were tested by WB. mRNA of HMGB-1, Biglycan, HAS1, HAS2 and HAS3 was detected by real-time PCR. The cytokines and chemokines were measured by ELISA.
Results
This result is corroborated by less tubular damage on rhALR treated rats than those on untreated rats. rhALR treated rats have significantly less apoptosis in tubular epithelial cells, less tubulointerstitial infiltration by neutrophils (24 h) and macrophages (72 h), as well as lower levels of inflammatory cytokines compared to the untreated control rats. Furthermore, rhALR downregulate mRNA expression of endogenous liagands for TLR4 and restrain activation of TLR4 and downstream signaling molecules (ERK, JNK and p38) on rats with renal I/R injury.
Conclusion
rhALR protects kidney from I/R injury by relieving the inflammatory responses via regulation of TLR4 signaling pathway.These results suggest that ALR might be used in the development of novel immune therapy for the renal IRI
rhALR protects kidney from I/R injury by regulation of TLR4 signaling pathway
Funding
- Government Support - Non-U.S.