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Melatonin Protects Human Renal Proximal Tubule Epithelial Cells Against High Glucose-Mediated Fibrosis via the Cellular Prion Protein-TGF-β-Smad Signaling Axis
- Source :
- International Journal of Medical Sciences
- Publication Year :
- 2020
- Publisher :
- Ivyspring International Publisher, 2020.
-
Abstract
- Diabetes-mediated hyperglycemia is a major risk factor for renal fibrosis, resulting in the development of chronic kidney diseases. To address this issue, the effect of melatonin, which has an antioxidative potential, on renal fibrosis in human renal proximal tubule epithelial cells under high glucose conditions was investigated. Under high glucose conditions, the generation of reactive oxygen species was drastically increased in human renal proximal tubule epithelial cells, which lead to the inhibition of cell proliferation, enlargement of cell size, reduction of cell survival, and suppression of antioxidant enzyme activities. High glucose also increased the expression of transforming growth factor-β, leading to an increase in Smad2 phosphorylation. These fibrotic phenotype changes increased the expression of fibrosis-mediated extracellular matrix proteins, such as fibronectin, collagen I, and α-smooth muscle actin. In addition, the level of cellular prion protein (PrPC), which is associated with several biological processes, was decreased by exposure to high glucose conditions. Melatonin recovered the expression levels of PrPC under high glucose conditions via phosphorylation of Akt, resulting in the prevention of high glucose-induced fibrosis. In particular, overexpression of PrPC blocked the high glucose-mediated fibrotic phenotype change. These findings indicate that melatonin could be a powerful agent for treating hyperglycemia-induced renal fibrosis.
- Subjects :
- Radioimmunoprecipitation Assay
Blotting, Western
melatonin
Collagen Type I
Prion Proteins
Extracellular matrix
Melatonin
Kidney Tubules, Proximal
03 medical and health sciences
0302 clinical medicine
Fibrosis
Transforming Growth Factor beta
Renal fibrosis
medicine
Humans
Phosphorylation
Protein kinase B
Cell Proliferation
biology
L-Lactate Dehydrogenase
Chemistry
Cell growth
fibrosis
General Medicine
Th1 Cells
medicine.disease
renal proximal tubule epithelial cells
Catalase
Cell biology
high glucose
Fibronectins
Fibronectin
cellular prion protein
Glucose
biology.protein
030211 gastroenterology & hepatology
medicine.drug
Research Paper
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 14491907
- Volume :
- 17
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- International Journal of Medical Sciences
- Accession number :
- edsair.doi.dedup.....79120ed109545ca7bf1da29b40f4b04b