Profile of Podocyte Translatome During Development of Type 2 and Type 1 Diabetic Nephropathy Using Podocyte-Specific TRAP mRNA RNA-seq

• Published in: Diabetes (New York, N.Y.) Vol. 70; no. 10; pp. 2377 - 2390
• Main Authors: Wang, Yinqiu, Niu, Aolei, Pan, Yu, Cao, Shirong, Terker, Andrew S, Wang, Suwan, Fan, Xiaofeng, Toth, Cynthia L, Ramirez Solano, Marisol A, Michell, Danielle L, Contreras, Danielle, Allen, Ryan M, Zhu, Wanying, Sheng, Quanhu, Fogo, Agnes B, Vickers, Kasey C, Zhang, Ming-Zhi, Harris, Raymond C
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.10.2021
• Subjects: Actin; Animals; Apoptosis; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - pathology; Diabetes Mellitus, Type 1 - complications; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - metabolism; Diabetic Nephropathies - genetics; Diabetic Nephropathies - metabolism; Diabetic Nephropathies - pathology; Diabetic nephropathy; Gene Expression Profiling; Genetics/Genomes/Proteomics/Metabolomics; Kidney diseases; Male; MAP kinase; Mice; Mice, Inbred C57BL; Mice, Knockout; mRNA; Nephropathy; Organ Specificity - genetics; Podocytes - metabolism; Podocytes - pathology; Protein Biosynthesis - genetics; Proteome - analysis; Proteome - genetics; Proteome - metabolism; RNA, Messenger - analysis; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA-Seq; Sequence Analysis, RNA; Signal transduction; Streptozocin; Transcriptome; Vascular endothelial growth factor receptors
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/DB21-0110

Podocyte injury is important in development of diabetic nephropathy (DN). Although several studies have reported single-cell-based RNA sequencing (RNA-seq) of podocytes in type 1 DN (T1DN), the podocyte translating mRNA profile in type 2 DN (T2DN) has not previously been compared with that of T1DN. We analyzed the podocyte translatome in T2DN in podocin-Cre; Rosa26 ; eNOS ; mice and compared it with that of streptozotocin-induced T1DN in podocin-Cre; Rosa26 ; eNOS mice using translating ribosome affinity purification (TRAP) and RNA-seq. More than 125 genes were highly enriched in the podocyte ribosome. More podocyte TRAP genes were differentially expressed in T2DN than in T1DN. TGF-β signaling pathway genes were upregulated, while MAPK pathway genes were downregulated only in T2DN, while ATP binding and cAMP-mediated signaling genes were downregulated only in T1DN. Genes regulating actin filament organization and apoptosis increased, while genes regulating VEGFR signaling and glomerular basement membrane components decreased in both type 1 and type 2 diabetic podocytes. A number of diabetes-induced genes not previously linked to podocyte injury were confirmed in both mouse and human DN. On the basis of differences and similarities in the podocyte translatome in T2DN and T1DN, investigators can identify factors underlying the pathophysiology of DN and novel therapeutic targets to treat diabetes-induced podocyte injury.