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PACS-2 attenuates diabetic kidney disease via the enhancement of mitochondria-associated endoplasmic reticulum membrane formation
- Source :
- Cell Death & Disease, Cell Death and Disease, Vol 12, Iss 12, Pp 1-12 (2021)
- Publication Year :
- 2021
- Publisher :
- Nature Publishing Group UK, 2021.
-
Abstract
- The altered homeostasis of mitochondria-associated endoplasmic reticulum (ER) membranes (MAM) was closely associated with the pathological process of nervous system diseases and insulin resistance. Here, the exact implication of phosphofurin acidic cluster sorting protein 2 (PCAS-2), an anchor protein in the MAM interface, in diabetic kidney disease was investigated. In the kidneys of type 1 and type 2 diabetes mice and HG-induced HK-2 cells, a notable disruption of ER-mitochondria interactions, accompanied by a decreased PACS-2 expression in all subcellular fractions. Furthermore, PACS-2 knockout mice with diabetes displayed accelerated development of proteinuria, deterioration of kidney function, and aggravated disruption of MAM area, ER stress, mitochondrial dysfunction, renal apoptosis, and fibrosis. However, overexpression of PACS-2 effectively protected diabetic kidneys and HG-treated HK-2 cells from renal tubular impairments. Importantly, experimental uncoupling of ER-mitochondria contacts reversed the protective effects of PACS-2 restoration on HK-2 cells under HG conditions. In summary, our data indicate a pivotal role of PACS-2 in the development of diabetic renal tubular injury via the stabilization of MAM.
- Subjects :
- Male
Cancer Research
medicine.medical_specialty
Immunology
Vesicular Transport Proteins
Mitochondrion
Endoplasmic Reticulum
Article
Cellular and Molecular Neuroscience
Mice
Diabetes complications
Fibrosis
Diabetes mellitus
Internal medicine
medicine
Animals
Humans
Diabetic Nephropathies
Endoplasmic reticulum membrane
QH573-671
Chemistry
Endoplasmic reticulum
Type 2 diabetes
Cell Biology
medicine.disease
Mitochondria
Endocrinology
Type 1 diabetes
Knockout mouse
Unfolded protein response
Cytology
Homeostasis
Subjects
Details
- Language :
- English
- ISSN :
- 20414889
- Volume :
- 12
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- Cell Death & Disease
- Accession number :
- edsair.doi.dedup.....293bea33b594a3ad9176bfcf317f0396