Alteration of autophagy-related protein 5 (ATG5) levels and Atg5 gene expression in diabetes mellitus with and without complications

Background Autophagy is a catabolic mechanism that involves lysosomal-dependent degradation of unnecessary intracellular components and responsible for normal cellular homeostasis. Autophagy pathway and its key participant ATG5/LC3 are associated with several pathologies such as diabetes mellitus an...

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Published in:	Diabetes & vascular disease research Vol. 18; no. 6; p. 14791641211062050
Main Authors:	Yassin, Remah, Tadmor, Hagar, Farber, Evgeny, Igbariye, Anas, Armaly-Nakhoul, Aida, Dahan, Inbal, Nakhoul, Farid, Nakhoul, Nakhoul
Format:	Journal Article
Language:	English
Published:	London, England SAGE Publications 01-11-2021
Subjects:	Animals Autophagy Autophagy-Related Protein 5 - genetics Diabetes Mellitus Diabetic Nephropathies - genetics Gene Expression Humans Leukocytes, Mononuclear Mice Original Key Indexing Terms: Diabetic Nephropathy, Retinopathy, Autophagy, Atg5, and LC3B Atg5 gene autophagy Diabetes Mellitus LC3B diabetic nephropathy
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Summary:	Background Autophagy is a catabolic mechanism that involves lysosomal-dependent degradation of unnecessary intracellular components and responsible for normal cellular homeostasis. Autophagy pathway and its key participant ATG5/LC3 are associated with several pathologies such as diabetes mellitus and its complications. Methods Levels and expression of autophagy key components ATG5 and LC3B were analyzed in both human model and murine tissues. One hundred and twenty human subjects were divided into four groups: Healthy (control), diabetes mellitus without complications, diabetic nephropathy, and diabetic retinopathy. Additionally, we used kidneys from WT healthy and diabetic nephropathy mice. Lysate derived from human peripheral blood mononuclear cells and murine renal cortex lysates were subjected to western blot and immunohistochemical analysis. Results Western blot and immunohistochemical analysis demonstrate that ATG5 protein levels were significantly decreased in diabetes mellitus, diabetic nephropathy (DN), and diabetic retinopathy patients versus healthy controls and in DN mice compared to healthy mice (0.65 ± 0.04; 1.15 ± 0.13 A.U. units, respectively). Quantification of staining area (%) of ATG5 mice tissue expression also decreased in DN versus healthy mice (4.42 ± 1.08%; 10.87 ± 1.01%, respectively). LC3B levels and expression Significant reduction in peripheral blood mononuclear cells in diabetic patients (with or without complications) vs. healthy controls. Renal LC3B levels were lower in DN versus healthy mice (0.36 ± 0.03; 0.68 ± 0.07 A.U. units). Renal LC3B staining quantification revealed significant reduction in DN versus healthy mice (1.7 ± 0.23%; 8.56 ± 1.7%). Conclusion We conclude that ATG5, as well as LC3B, are down regulated in diabetic patients with or without complications. This diminution contributes to deficiencies in the autophagy process.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Equal contribution
ISSN:	1479-1641 1752-8984 1752-8984
DOI:	10.1177/14791641211062050