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Overexpressing STAMP2 attenuates diabetic renal injuries via upregulating autophagy in diabetic rats.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2021 Nov 19; Vol. 579, pp. 47-53. Date of Electronic Publication: 2021 Sep 20. - Publication Year :
- 2021
-
Abstract
- Diabetic nephropathy (DN) is one of the most serious and major renal complications of diabetes. Previously, Six-transmembrane Protein of Prostate 2 (STAMP2) was reported to contribute to nutritional stress. The purpose of this study is to investigate whether overexpression of STAMP2 attenuates diabetic renal injuries in DN rats. We induced the DN rat model by high-fat diet and low-dose streptozotocin and evaluated the metabolite and urine albumin/creatinine. Recombinant adeno-associated virus vectors were injected for overexpression of STAMP2. Pathophysiologic and ultrastructure features of DN by histochemical stain and transmission electron microscope, autophagy-related proteins and signaling pathway by western blotting were assessed. We found the expression of STAMP2 was decreased and autophagy was blunted in DN rat kidneys. Overexpressing STAMP2 significantly ameliorated metabolic disturbance, insulin resistance, and specifically restoring diabetic renal injury. Furthermore, overexpressing STAMP2 improved the autophagy deficiency in DN rats, as revealed by changes in the expressions of Beclin1, p62, and LC3. Furthermore, STAMP2 overexpressing promoted autophagy by inhibiting the mTOR and activating the AMPK/SIRT1 signaling pathway. Our results suggested that STAMP2 overexpression attenuated renal injuries via upregulating autophagy in DN rats. STAMP2 overexpressing promoted autophagy may been involved with inhibition of the mTOR/ULK1 and activation of the AMPK/SIRT1 signaling pathway.<br /> (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Autophagy-Related Protein-1 Homolog biosynthesis
Diabetes Mellitus, Experimental
Diet, High-Fat
Genetic Vectors
Kidney Cortex pathology
Male
Rats
Rats, Sprague-Dawley
Signal Transduction
Sirtuin 1 biosynthesis
Streptozocin
TOR Serine-Threonine Kinases biosynthesis
Transcriptional Activation
Up-Regulation
Autophagy
Diabetic Nephropathies metabolism
Gene Expression Regulation
Kidney injuries
Membrane Proteins biosynthesis
Oxidoreductases biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 579
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 34583195
- Full Text :
- https://doi.org/10.1016/j.bbrc.2021.09.026