首页|Hyperuricemia induces liver injury by upregulating HIF-1a and inhibiting arginine biosynthesis pathway in mouse liver and human L02 hepatocytes
Hyperuricemia induces liver injury by upregulating HIF-1a and inhibiting arginine biosynthesis pathway in mouse liver and human L02 hepatocytes
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NSTL
The molecular mechanisms of uric acid (UA)-induced liver injury has not been clearly elucidated。 In this study， we aimed to investigate the effect and action mechanisms of UA in liver injury。 We analyzed the damaging effect of UA on mouse liver and L02 cells and subsequently performed metabolomics studies on L02 cells to identify abnormal metabolic pathways。 Finally， we verified transcription factors that regulate related metabolic enzymes。 UA directly activated the hepatic NLRP3 inflammasome and Bax apoptosis pathway in vivo and in vitro。 Related metabolites in the arginine biosynthesis pathway (or urea cycle)， L-arginine and L-argininosuccinate were decreased， and ammonia was increased in UA-stimulated L02 cells， which was mediated by carbamoyl phosphate synthase 1 (CPS1)， argininosuccinate synthase (ASS) and argininosuccinate lyase (ASL) downregulation。 UA upregulated hypoxia inducible factor-lalpha (HIF-la) in vivo and in vitro， and HIF-la inhibition alleviated the UA-induced ASS downregulation and hepatocyte injury。 In conclusion， UA upregulates HIF-la and inhibits urea cycle enzymes (UCEs)。 This leads to liver injury， with evidence of hepatocyte inflammation， apoptosis and oxidative stress。
Uric acidLiver injuryASSHIF-1a
Lei Huang、Xinyu He、Wen Peng、Xueqing He、Bei Xu、Hu Xu、Yaoxing Wang、Wenjun Xu、Wentong Chen、Sheng Wang、Lanlan Zhou、Ning Liu、Youzhi Xu、Wenjie Lu
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Basic Medical College, Anhui Medical University, Hefei, 230032, China
2022
Biochemical and Biophysical Research Communications
NSTL
