Protease-Activated Receptor-2 and Phospholipid Metabolism Analysis in Hyperuricemia-Induced Renal Injury

Author:

Sui Xiaolu1ORCID,Xie Tingfei2ORCID,Xu Yunpeng1ORCID,Zhang Aisha1ORCID,Zhang Yanzi1ORCID,Gu Fengjuan3ORCID,Li Lixiang1ORCID,Xu Zibin2ORCID,Chen Jihong12ORCID

Affiliation:

1. Department of Nephrology, The Second Affiliated Hospital of Shenzhen University, Shenzhen 518000, Guangdong, China

2. Department of Nephrology, The People’s Hospital of Baoan Shenzhen, The Second School of Clinical Medicine, Southern Medical University, Shenzhen 518000, Guangdong, China

3. Department of Nephrology, Shenzhen Baoan People’s Hospital (Group) The Second People’s Hospital, Shenzhen 518000, Guangdong, China

Abstract

Interstitial inflammation is an important mechanism of pathological damage in renal injury caused by hyperuricemia. Protease-activated receptor-2 (PAR2) is a class of targets that act upstream of the PI3K/AKT/NF-κB pathway and is involved in various inflammatory diseases. We induced a hyperuricemia model in rats by adenine and ethambutol gavage in an in vivo experiment. We demonstrated that PAR2 and PI3K/AKT/NF-κB pathway expression were significantly upregulated in renal tissues, with massive inflammatory cell infiltration in the renal interstitium and renal tissue injury. Treating hyperuricemic rats with AZ3451, a selective metabotropic antagonist of PAR2, we demonstrated that PAR2 antagonism inhibited the PI3K/AKT/NF-κB pathway and attenuated tubular dilation and tubulointerstitial inflammatory cell infiltration. The phospholipid metabolism profiles provided a perfect separation between the normal and hyperuricemic rats. In addition, we also found that AZ3451 can affect phospholipid metabolism. Our work suggests that PAR2 may mediate hyperuricemia-mediated renal injury by activating the PI3K/AKT/NF-κB pathway. The PAR2 antagonist AZ3451 may be a promising therapeutic strategy for hyperuricemia-induced inflammatory responses.

Funder

Science and Technology Planning Project of Shenzhen Municipality

Publisher

Hindawi Limited

Subject

Cell Biology,Immunology

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