TY - JOUR
TI - Proteomic Analysis of Mouse Kidney Tissue Associates Peroxisomal
Dysfunction with Early Diabetic Kidney Disease
AU - Tserga, Aggeliki
AU - Pouloudi, Despoina
AU - Saulnier-Blache, Jean
AU - Sebastien
AU - Stroggilos, Rafael
AU - Theochari, Irene
AU - Gakiopoulou,
AU - Harikleia
AU - Mischak, Harald
AU - Zoidakis, Jerome
AU - Schanstra, Joost
AU - Peter
AU - Vlahou, Antonia
AU - Makridakis, Manousos
JO - BioMedicine
PY - 2021
VL - 10
TODO - 2
SP - null
PB - MDPI
SN - 2211-8039
TODO - 10.3390/biomedicines10020216
TODO - diabetes; diabetic kidney disease; proteomics; kidney; LC-MS; MS;
biomarker; peroxisome; glomeruli
TODO - Background: The absence of efficient inhibitors for diabetic kidney
disease (DKD) progression reflects the gaps in our understanding of DKD
molecular pathogenesis. Methods: A comprehensive proteomic analysis was
performed on the glomeruli and kidney cortex of diabetic mice with the
subsequent validation of findings in human biopsies and omics datasets,
aiming to better understand the underlying molecular biology of early
DKD development and progression. Results: LC-MS/MS was employed to
analyze the kidney proteome of 2 DKD models: Ins2Akita (early and late
DKD) and db/db mice (late DKD). The abundance of detected proteins was
defined. Pathway analysis of differentially expressed proteins in the
early and late DKD versus the respective controls predicted
dysregulation in DKD hallmarks (peroxisomal lipid metabolism and
beta-oxidation), supporting the functional relevance of the findings.
Comparing the observed protein changes in early and late DKD, the
consistent upregulation of 21 and downregulation of 18 proteins was
detected. Among these were downregulated peroxisomal and upregulated
mitochondrial proteins. Tissue sections from 16 DKD patients were
analyzed by IHC confirming our results. Conclusion: Our study shows an
extensive differential expression of peroxisomal proteins in the early
stages of DKD that persists regardless of the disease severity,
providing new perspectives and potential markers of diabetic kidney
dysfunction.
ER -