mmpc-logo mmpc-logo
twitter-logo    bluesky-logo
| Create Account | login
Publication
Renal Angptl4 is a key fibrogenic molecule in progressive diabetic kidney
disease.
Authors Srivastava SP, Zhou H, Shenoi R, Morris M, Lainez-Mas B, Goedeke L, Rajendran
BK, Setia O, Aryal B, Kanasaki K, Koya D, Inoki K, Dardik A, Bell T,
Fernández-Hernando C, Shulman GI, Goodwin JE
Submitted By Submitted Externally on 2/7/2025
Status Published
Journal Science advances
Year 2024
Date Published 12/1/2024
Volume : Pages 10 : eadn6068
PubMed Reference 39630889
Abstract Angiopoietin-like 4 (ANGPTL4), a key protein involved in lipoprotein metabolism,
has diverse effects. There is an association between Angptl4 and diabetic kidney
disease; however, this association has not been well investigated. We show that
both podocyte- and tubule-specific ANGPTL4 are crucial fibrogenic molecules in
diabetes. Diabetes accelerates the fibrogenic phenotype in control mice but not
in ANGPTL4 mutant mice. The protective effect observed in ANGPTL4 mutant mice is
correlated with a reduction in stimulator of interferon genes pathway
activation, expression of pro-inflammatory cytokines, reduced
epithelial-to-mesenchymal transition and endothelial-to-mesenchymal transition,
lessened mitochondrial damage, and increased fatty acid oxidation.
Mechanistically, we demonstrate that podocyte- or tubule-secreted Angptl4
interacts with Integrin ß1 and influences the association between dipeptidyl-4
with Integrin ß1. We demonstrate the utility of a targeted pharmacologic therapy
that specifically inhibits Angptl4 gene expression in the kidneys and protects
diabetic kidneys from proteinuria and fibrosis. Together, these data demonstrate
that podocyte- and tubule-derived Angptl4 is fibrogenic in diabetic kidneys.




Menu

Home
Contact
About MMPC
Animal Husbandry
Tests Data
Search Data
Analysis
Clients
MMPC Centers

Newsletter

Interested in receiving MMPC News?
twitter-logo Mouse Phenotyping
@NationalMMPC



2017 National MMPC. All Rights Reserved.