Profiling of insulin-resistant kidney models and human biopsies reveals common and cell-type-specific mechanisms underpinning Diabetic Kidney Disease
Year: 2024
Type: article
Abstract: 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.
Source: Nature Communications
Authors: Abigail C. Lay, Van Du T. Tran, Viji Nair, Virginie Betin, Jennifer A. Hurcombe, Alexandra F. Barrington, Robert JP Pope, Frédéric Burdet, Florence Mehl, Dmytro Kryvokhyzha, Abrar Ahmad, Matthew C. Sinton, Philip Lewis, Marieangela C. Wilson, Rajasree Menon, Edgar Otto, Kate J. Heesom, Mark Ibberson, Helen C. Looker, Robert G. Nelson, Wenjun Ju, Matthias Kretzler, Simon C. Satchell, Maria F. Gomez, Richard J. M. Coward, Wenjun Ju, Matthias Kretzler
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,790
Funders: European Federation of Pharmaceutical Industries and Associations, Kidney Research UK, European Commission, Stiftelsen för Strategisk Forskning, Hjärt-Lungfonden, Vetenskapsrådet, Horizon 2020 Framework Programme, Medical Research Council, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: Harvard Chronic Kidney Disease Research Biopsy Center, Central Hub for Kidney Precision Medicine, G2004031785, PREcision Medicine through IntErrogation of Rna in the kidnEy (PREMIERE), G263730981, Chronic Kidney Disease Precision Medicine Project, G342316341, University of Michigan O'Brien Kidney Translational Core Center, Identifying New Molecular Pathways and Therapeutic Targets in Diabetic Kidney Disease, G434337789, Nephron Sub-segmental Omics and Quantitative 3D Imaging of Human Kidney., AKI Matched Phenotype Linked Evaluation with Tissue (AMPLE-Tissue), G5049997570, Multidimensional cellular interrogation of the kidney in AKI and CKD, Biomarker Enterprise to Attack DKD - Sofia ref.: 115974, Phenotyping REnal Cases In Sepsis and surgery for Early Acute Kidney Injury (PReCISE AKI), G6037130591, Is Diabetic Nephropathy the Result of a Podocyte Tauopathy?, Cleveland Precision Medicine Chronic Kidney Disease Cohort, Kidney Precision Medicine Program (KPMP): Columbia AKI Recruitment Site, G712881263, Novel molecular mechanisms underlying diabetic complications, Spatial Metabolomics for Human Kidneys, Single-nucleus sequencing and in situ mapping of mRNA molecules in human kidney, Spatial Elucidation of Human Acute Kidney Injury and Chronic Kidney Disease using Imaging Mass Cytometry, PREcision Medicine through IntErrogation of Rna in the kidnEy (PREMIERE), Michigan Diabetes Research Center (MDRC), Minnesota Precision Medicine CKD & Resilient Diabetes Recruiting Site: Engagement, Enrollment & Ethics, Integrated spatial interrogation of cellular and molecular signatures of human kidney disease, Single cell multiomic and spatial atlas of acute and chronic kidney injury, Mount Sinai Health System Kidney Precision Medicine Project, University of Illinois at Chicago KPMP CKD Recruitment Site, AKI Matched Phenotype Linked Evaluation with Tissue (AMPLE-Tissue), Central Hub for Kidney Precision Medicine, Multimodal Imaging Mass Spectrometry and Spatial Omics for the Human Kidney, Boston Chronic Kidney Disease Research Biopsy Center, Cleveland Precision Medicine Chronic Kidney Disease Cohort, Kidney Precision Medicine Project - Patient Engagement, KPMP Kidney Mapping and Atlas Project (KMAP), Geographic and Environmental Health Equity in Kidney Precision Medicine, Spatial Multi-Omics to Profile Metabolic Pathways for Kidney Disease, Spatial Mapping of Proteomic and Transcriptional Signatures in Kidney Disease, Insulin signalling to the podocyte; pathological importance and therapeutic potential.
OpenAlex ID: W4404496352