2. Academic Validation
  3. GPR108 deficiency promotes urate-induced renal interstitial fibrosis

GPR108 deficiency promotes urate-induced renal interstitial fibrosis

  • Cell Signal. 2025 Sep 12:136:112129. doi: 10.1016/j.cellsig.2025.112129.
Deping Xu 1,  Ping Yang 2,  Wei Song 2,  Kainan Liao 2,  Dandan Zang 3,  Qiang Zhou 4,  Haisheng Zhou 5
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, China; The Clinical Laboratory, the Second People's Hospital of Hefei, The Affiliated Hefei Hospital of Anhui Medical University, Hefei, China.
  • 2 Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, China.
  • 3 Center for Scientific Research, Anhui Medical University, Hefei, China.
  • 4 The Clinical Laboratory, the Second Affiliated Hospital of Anhui Medical University, Hefei, China. Electronic address: zhouqiang1973@163.com.
  • 5 Department of Biochemistry and Molecular Biology, Anhui Medical University, Hefei, China; The Clinical Laboratory, the Second Affiliated Hospital of Anhui Medical University, Hefei, China. Electronic address: haishengs@ahmu.edu.cn.
PMID: 40946943 DOI: 10.1016/j.cellsig.2025.112129
Abstract

Uric acid, a product of purine metabolism, is predominantly excreted via the kidneys. Chronic hyperuricemia, often driven by high-purine diets, contributes to renal injury marked by inflammation, tubular damage, and interstitial fibrosis with epithelial-mesenchymal transition (EMT). G protein-coupled receptor 108 (GPR108), a negative regulator of NF-κB-mediated inflammation, remains unexplored in hyperuricemia-induced chronic kidney disease (CKD). This study investigates GPR108's role in uric acid nephropathy using adenine-fed mice and in vitro models. Gpr108-deficient mice exhibited aggravated renal fibrosis, EMT activation, and elevated cytokine levels compared to controls. In vitro, renal tubular epithelial cells of primary cultured Gpr108 knockout mice heightened sensitivity to uric acid-induced EMT, accompanied by increased TGF-β1 production and NF-κB activation. These findings demonstrate that GPR108 deficiency exacerbates renal inflammation and fibrosis by amplifying NF-κB-driven EMT and TGF-β1 signaling. Our study identifies GPR108 as a protective modulator in hyperuricemia-induced CKD, highlighting its potential as a therapeutic target to mitigate renal interstitial fibrosis.

Keywords

Chronic kidney disease; Epithelial-mesenchymal transition; GPR108; Hyperuricemia; Renal interstitial fibrosis; Uric acid.

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