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Upregulation of CKIP - 1 inhibits high-glucose induced inflammation and oxidative stress in HRECs and attenuates diabetic retinopathy by modulating Nrf2 / ARE signaling pathway: an in vitro study.
- Source :
-
Cell & bioscience [Cell Biosci] 2019 Aug 23; Vol. 9, pp. 67. Date of Electronic Publication: 2019 Aug 23 (Print Publication: 2019). - Publication Year :
- 2019
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Abstract
- Purpose: The aim of this study was to investigate the underlying mechanisms of diabetic retinopathy (DR) development.<br />Methods: Real-Time qPCR was used to detect Casein kinase 2 interacting protein - 1 ( CKIP - 1 ) and Nuclear factor E2 - related factor 2 ( Nrf2 ) mRNA levels. Western Blot was employed to detect protein levels. Malondialdehyde (MDA) assay kit, superoxide dismutase (SOD) kit and glutathione peroxidase (GSH-Px) kit were used to evaluate oxidative stress in high-glucose treated human retinal endothelial cells (HRECs). Calcein-AM/propidium iodide (PI) double stain kit was employed to detect cell apoptosis. Enzyme-linked ImmunoSorbent Assay (ELISA) was used to detect inflammation associated cytokines secretion. Co-immunoprecipitation (CO-IP) was performed to investigate the interactions between CKIP - 1 and Nrf2 . Luciferase reporter gene system was used to detect the transcriptional activity of Nrf2 .<br />Results: CKIP - 1 was significantly downregulated in either DR tissues or high-glucose treated HRECs comparing to the Control groups. Besides, high-glucose (25 mM) inhibited HRECs viability and induced oxidative stress, inflammation associated cytokines (TNF-α, IL-6 and IL-1β) secretion and cell apoptosis, which were all reversed by synergistically overexpressing CKIP - 1 and aggravated by knocking down CKIP - 1 . Of note, we found that overexpressed CKIP - 1 activated Nrf2 / ARE signaling pathway and increased its downstream targets including HO - 1 , NQO - 1 , γGCS and SOD in high-glucose treated HRECs. Further results also showed that CKIP - 1 regulated cell viability, oxidative stress, inflammation and apoptosis in high-glucose treated HRECs by activating Nrf2 / ARE signaling pathway.<br />Conclusion: We concluded that overexpressed CKIP - 1 alleviated DR progression by activating Nrf2 / ARE signaling pathway.<br />Competing Interests: Competing interestsThe authors declare that they have no competing interests.
Details
- Language :
- English
- ISSN :
- 2045-3701
- Volume :
- 9
- Database :
- MEDLINE
- Journal :
- Cell & bioscience
- Publication Type :
- Academic Journal
- Accession number :
- 31462987
- Full Text :
- https://doi.org/10.1186/s13578-019-0331-x