Lay Abigail C, Tran Van Du T, Nair Viji, Betin Virginie, Hurcombe Jennifer A, Barrington Alexandra F, Pope Robert Jp, Burdet Frédéric, Mehl Florence, Kryvokhyzha Dmytro, Ahmad Abrar, Sinton Matthew C, Lewis Philip, Wilson Marieangela C, Menon Rajasree, Otto Edgar, Heesom Kate J, Ibberson Mark, Looker Helen C, Nelson Robert G, Ju Wenjun, Kretzler Matthias, Satchell Simon C, Gomez Maria F, Coward Richard J M
Bristol Renal, Bristol Medical School, University of Bristol, Bristol, UK.
Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Nat Commun. 2024 Nov 19;15(1):10018. doi: 10.1038/s41467-024-54089-1.
Diabetic kidney disease (DKD) is the leading cause of end stage kidney failure worldwide, of which cellular insulin resistance is a major driver. Here, we study key human kidney cell types implicated in DKD (podocytes, glomerular endothelial, mesangial and proximal tubular cells) in insulin sensitive and resistant conditions, and perform simultaneous transcriptomics and proteomics for integrated analysis. Our data is further compared with bulk- and single-cell transcriptomic kidney biopsy data from early- and advanced-stage DKD patient cohorts. We identify several consistent changes (individual genes, proteins, and molecular pathways) occurring across all insulin-resistant kidney cell types, together with cell-line-specific changes occurring in response to insulin resistance, which are replicated in DKD biopsies. This study provides a rich data resource to direct future studies in elucidating underlying kidney signalling pathways and potential therapeutic targets in DKD.
糖尿病肾病（DKD）是全球终末期肾衰竭的主要原因，其中细胞胰岛素抵抗是主要驱动因素。在此，我们研究了在胰岛素敏感和抵抗条件下与DKD相关的关键人类肾细胞类型（足细胞、肾小球内皮细胞、系膜细胞和近端肾小管细胞），并同时进行转录组学和蛋白质组学分析以进行综合分析。我们的数据进一步与早期和晚期DKD患者队列的大量和单细胞转录组肾活检数据进行了比较。我们确定了所有胰岛素抵抗肾细胞类型中出现的几个一致变化（单个基因、蛋白质和分子途径），以及因胰岛素抵抗而发生的细胞系特异性变化，这些变化在DKD活检中得到了重现。本研究提供了丰富的数据资源，以指导未来阐明DKD潜在肾信号通路和治疗靶点的研究。
