2. Academic Validation
  3. Microbial imidazole propionate affects glomerular filtration rate in patients with diabetic nephropathy through association with HSP90α

Microbial imidazole propionate affects glomerular filtration rate in patients with diabetic nephropathy through association with HSP90α

  • Biochim Biophys Acta Mol Cell Res. 2024 Mar 5:119703. doi: 10.1016/j.bbamcr.2024.119703.
Dan Lv 1,  Wenhan Zheng 2,  Zheng Zhang 2,  Ziyue Lin 2,  Keqian Wu 2,  Handeng Liu 3,  Xiaohui Liao 4,  Yan Sun 5
Affiliations

Affiliations

  • 1 Department of Nephrology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China; Department of Neuroscience Research Center, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China.
  • 2 Department of Neuroscience Research Center, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China.
  • 3 Laboratory of Tissue and Cell Biology, Experimental Teaching Center, Chongqing Medical University, Chongqing 400016, China.
  • 4 Department of Nephrology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China. Electronic address: lxh@hospital.cqmu.edu.cn.
  • 5 Department of Neuroscience Research Center, School of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China. Electronic address: yansun@cqmu.edu.cn.
PMID: 38453032 DOI: 10.1016/j.bbamcr.2024.119703
Abstract

Imidazole propionate (ImP) is a detrimental metabolite produced by the fermentation of histidine intermediates via the intestinal flora. Here, the untargeted metabolite analysis of plasma metabolites from patients with diabetic nephropathy (DN), in combination with the Human Metabolome Database, revealed significantly increased levels of ImP in patients with DN, with a positive correlation with patients' blood creatinine concentration and urinary albumin-to-creatinine ratio, and a negative correlation with the glomerular filtration rate. RNA-seq was applied to detect the effects of ImP on renal tissue transcriptome in mice with DN. It demonstrated that ImP exacerbated renal injury in mice with DN and promoted renal tubular epithelial-mesenchymal transition (EMT), leading to renal mesenchymal fibrosis and renal impairment. Furthermore, ImP was found to directly target HAP90α and activate the PI3K-Akt signalling pathway, which is involved in EMT, by the drug affinity response target stability method. The findings showed that ImP may provide a novel target for DN quality, as it can directly bind to and activate HSP90, thereby facilitating the development of DN while acting as a potential indicator for the clinical diagnosis of DN.

Keywords

Diabetic nephropathy; EMT; Fibrosis; Gut microbiota metabolites; Imidazole propionate.

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