1. AMP-activated protein kinase α2 contributes to acute and chronic hyperuricemic nephropathy via renal urate deposition in a mouse model.
- Author
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Yang C, Su HY, An N, Wu HL, Guo XY, Li ZH, Chen XC, Zhu SP, Wu D, Li HY, Pan QJ, Liang D, and Liu HF
- Subjects
- AMP-Activated Protein Kinases genetics, Animals, Disease Models, Animal, Fibrosis, Kidney pathology, Mice, Mice, Knockout, Uric Acid adverse effects, Uric Acid metabolism, AMP-Activated Protein Kinases metabolism, Hyperuricemia chemically induced, Hyperuricemia genetics, Kidney Diseases genetics, Kidney Diseases metabolism, Kidney Failure, Chronic
- Abstract
Hyperuricemia can induce acute and chronic kidney damage, but the pathological mechanism remains unclear. The potential role of AMP-activated protein kinase (AMPK) α2 in hyperuricemia-induced renal injury was investigated in this study. Acute and chronic hyperuricemic nephropathy was induced by administering intraperitoneal injections of uric acid and oxonic acid to AMPK α2 knockout and wild-type mice. Changes in renal function, histopathology, inflammatory cell infiltration, renal interstitial fibrosis, and urate deposition were analyzed. In both acute and chronic hyperuricemic nephropathy mouse models, knockout of AMPK α2 significantly reduced serum creatinine levels and renal pathological changes. The tubular expression of kidney injury molecule-1 was also reduced in hyperuricemic nephropathy mice deficient in AMPK α2. In addition, knockout of AMPK α2 significantly suppressed the infiltration of renal macrophages and progression of renal interstitial fibrosis in mice with chronic hyperuricemic nephropathy. Knockout of AMPK α2 reduced renal urate crystal deposition, probably through increasing the expression of the uric acid transporter, multidrug resistance protein 4. In summary, AMPK α2 is involved in acute and chronic hyperuricemia-induced kidney injury and may be associated with increased urate crystal deposition in the kidney., (© 2022. The Author(s).)
- Published
- 2022
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