Comparison of Kidney Transcriptomic Profiles of Early and Advanced Diabetic Nephropathy Reveals Potential New Mechanisms for Disease Progression.

Abstract

To identify the factors mediating the progression of diabetic nephropathy (DN), we performed RNA sequencing of kidney biopsy samples from patients with early DN, advanced DN, and normal kidney tissue from nephrectomy samples. A set of genes that were upregulated at early but downregulated in late DN were shown to be largely renoprotective, which included genes in the retinoic acid pathway and glucagon-like peptide 1 receptor. Another group of genes that were downregulated at early but highly upregulated in advanced DN consisted mostly of genes associated with kidney disease pathogenesis, such as those related to immune response and fibrosis. Correlation with estimated glomerular filtration rate (eGFR) identified genes in the pathways of iron transport and cell differentiation to be positively associated with eGFR, while those in the immune response and fibrosis pathways were negatively associated. Correlation with various histopathological features also identified the association with the distinct gene ontological pathways. Deconvolution analysis of the RNA sequencing data set indicated a significant increase in monocytes, fibroblasts, and myofibroblasts in advanced DN kidneys. Our study thus provides potential molecular mechanisms for DN progression and association of differential gene expression with the functional and structural changes observed in patients with early and advanced DN.

• Authors: Ying Fan, Zhengzi Yi, Vivette D D'Agati, Zeguo Sun, Fang Zhong, Weijia Zhang, Jiejun Wen, Ting Zhou, Ze Li, Li He, Qunzi Zhang, Kyung Lee, John Cijiang He, Niansong Wang
• Journal: Diabetes (Diabetes) Vol. 68 Issue 12 Pg. 2301-2314 (12 2019) ISSN: 1939-327X [Electronic] United States
• PMID: 31578193 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2019 by the American Diabetes Association.

Topics

• Diabetic Nephropathies (genetics, metabolism, pathology)
• Disease Progression
• Gene Expression Profiling
• Gene Expression Regulation
• Glomerular Filtration Rate (physiology)
• Humans
• Kidney (metabolism, pathology)
• Transcriptome