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Profile of Podocyte Translatome During Development of Type 2 and Type 1 Diabetic Nephropathy Using Podocyte-Specific TRAP mRNA RNA-seq.
- Source :
- Diabetes; Oct2021, Vol. 70 Issue 10, p2377-2390, 14p
- Publication Year :
- 2021
-
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; Rosa26fsTRAP; 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- DIABETIC nephropathies
RNA sequencing
CELLULAR signal transduction
DRUG target
BASAL lamina
RNA metabolism
RNA analysis
PROTEINS
RESEARCH
SEQUENCE analysis
ANIMAL experimentation
RESEARCH methodology
DIABETES
TYPE 1 diabetes
RNA
MEDICAL cooperation
EVALUATION research
PROTEOMICS
TYPE 2 diabetes
COMPARATIVE studies
GENE expression profiling
IMMUNITY
RESEARCH funding
EPITHELIAL cells
MICE
DISEASE complications
Subjects
Details
- Language :
- English
- ISSN :
- 00121797
- Volume :
- 70
- Issue :
- 10
- Database :
- Complementary Index
- Journal :
- Diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 152790658
- Full Text :
- https://doi.org/10.2337/db21-0110