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

作者全名：Lv, Dan; Zheng, Wenhan; Zhang, Zheng; Lin, Ziyue; Wu, Keqian; Liu, Handeng; Liao, Xiaohui; Sun, Yan

作者地址：[Lv, Dan; Liao, Xiaohui] Chongqing Med Univ, Affiliated Hosp 2, Dept Nephrol, Chongqing 400010, Peoples R China; [Lv, Dan; Zheng, Wenhan; Zhang, Zheng; Lin, Ziyue; Wu, Keqian; Sun, Yan] Chongqing Med Univ, Dept Neurosci Res Ctr, Sch Basic Med Sci, Chongqing 400016, Peoples R China; [Liu, Handeng] Chongqing Med Univ, Expt Teaching Ctr, Lab Tissue & Cell Biol, Chongqing 400016, Peoples R China

通信作者：Liao, XH (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Nephrol, Chongqing 400010, Peoples R China.; Sun, Y (通讯作者)，Chongqing Med Univ, Dept Neurosci Res Ctr, Sch Basic Med Sci, Chongqing 400016, Peoples R China.

来源：BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001201719300001

JCR分区：Q1

影响因子：4.6

年份：2024

卷号：1871

期号：4

开始页：　

结束页：　

文献类型：Article

关键词：Gut microbiota metabolites; Imidazole propionate; Diabetic nephropathy; EMT; Fibrosis

摘要：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 HAP90 alpha 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.

基金机构：National Natural Science Foundation of China [82270876, 81970702]; Natural Science Foundation of Chongqing [CSTB2022NSCQ-MSX0126]

基金资助正文：This work was supported by National Natural Science Foundation of China Grant 82270876 and 81970702 (to Zheng Zhang) , Natural Science Foundation of Chongqing Grant CSTB2022NSCQ-MSX0126 (to Zheng Zhang) .