1. Profile of Podocyte Translatome During Development of Type 2 and Type 1 Diabetic Nephropathy Using Podocyte-Specific TRAP mRNA RNA-seq.
- Author
-
Wang Y, Niu A, Pan Y, Cao S, Terker AS, Wang S, Fan X, Toth CL, Ramirez Solano MA, Michell DL, Contreras D, Allen RM, Zhu W, Sheng Q, Fogo AB, Vickers KC, Zhang MZ, and Harris RC
- Subjects
- Animals, 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 pathology, Gene Expression Profiling, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Organ Specificity genetics, 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, Streptozocin, Transcriptome, Diabetic Nephropathies genetics, Diabetic Nephropathies metabolism, Podocytes metabolism
- Abstract
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
fsTRAP ; eNOS-/- ; db/db mice and compared it with that of streptozotocin-induced T1DN in podocin-Cre; Rosa26fsTRAP ; 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., (© 2021 by the American Diabetes Association.)- Published
- 2021
- Full Text
- View/download PDF