Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 125, Issue -, Pages -Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2020.109924
Keywords
miR-130a; Retinal pigment epithelium; SOD1; ROS; Pyroptosis
Funding
- National Natural Science Foundation of China [81060077]
- Internal Research Institutions for Scientific Research Projects of Yunnan Medical and Health Institute [2014NS183, 2018NS0145]
- Applied Fundamental Research of Yunnan Province [2017FE468(-175), 2017FE468(-046)]
- Bethune-Lang Mu Ophthalmological Research Fund for Middle-aged and Young Researchers [BJ-LM2017006L]
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High-glucose induced retinal pigment epithelium (RPE) death by triggering oxidative stress, however, the underlying mechanisms are still not fully delineated. In this study, the RPE cell line ARPE-19 were treated with different concentrations of glucose, the results showed that high-glucose (50 mM) inhibited cell proliferation, promoted cell apoptosis and reactive oxygen species (ROS) production in a time-dependent manner. Notably, we found that high-glucose (50 mM) increased the expression levels of Caspase-1, Gasdermin D, NLRP3, IL-1 beta and IL-18 in ARPE-19 cells, which indicated that high-glucose triggered pyroptotic cell death. Further results validated that both ROS scavenger N-acetyl cysteine (NAC) and pyroptosis inhibitor necrosulfonamide (NSA) reversed the effects of high-glucose (50 mM) on ARPE-19 cell proliferation, apoptosis and pyroptosis. In addition, high-glucose (50 mM) significantly decreased the levels of miR-130a and superoxide dismutase (SOD) 1, and promoted tumor necrosis factor (TNF)-alpha expressions in ARPE-19 cells. Interestingly, upregulation of miR-130a increased SOD1 levels in a TNF-alpha dependent manner. Furthermore, overexpression of miR-130a abrogated the effects of high-glucose (50 mM) on the above cell functions, which were all reversed by either upregulating TNF-alpha or knocking down SOD1 in ARPE-19 cells. Taken together, upregulation of miR-130a alleviated the cytotoxic effects of high-glucose (50 mM) on ARPE-19 cells by regulating TNF-alpha/SOD1/ROS axis mediated pyroptotic cell death.
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