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• W3018968275 abstract "Diabetic retinopathy (DR) is one of the hallmark complications of diabetes and a leading cause of vision loss in adults. Retinal pericyte death seems to be a prominent feature in the onset of DR. Pyroptosis is an inflammatory form of programmed cell death, defined as being caspase-gasdermin-D (GSDMD)-dependent. The NOD-like receptor pyrin 3 (NLRP3) inflammasome plays an important role in mediating GSDMD activation. However, the role and mechanism of pyroptosis in the loss of retinal pericytes during the pathogenesis of DR are still unclear. In the present study, we cultured primary human retinal pericytes (HRPs) in high glucose medium; caspase-3 inhibitor DEVD, caspase-1 inhibitor YVAD, or NLRP3 inhibitor glyburide was used as intervention reagents; GSDMD was overexpressed or suppressed by transfection with an expressing vector or retroviral silencing of GSDMD, respectively. Our data showed that high glucose induced NLRP3-caspase-1-GSDMD activation and pore formation in a dose- and time-dependent manner (<mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML id=M1><mml:mi>p</mml:mi><mml:mo><</mml:mo><mml:mn>0.05</mml:mn></mml:math>) and resulted in the inflammatory cytokines IL-1 β and IL-18 and lactate dehydrogenase (LDH) release from HRPs (<mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML id=M2><mml:mi>p</mml:mi><mml:mo><</mml:mo><mml:mn>0.05</mml:mn></mml:math>), which are all signs of HRP pyroptosis. Overexpression of GSDMD facilitated high glucose-induced pyroptosis (all <mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML id=M3><mml:mi>p</mml:mi><mml:mo><</mml:mo><mml:mn>0.05</mml:mn></mml:math>). However, these effects were blunted by synergistically treating DEVD, YVAD, and silencing GSDMD (<mml:math xmlns:mml=http://www.w3.org/1998/Math/MathML id=M4><mml:mi>p</mml:mi><mml:mo><</mml:mo><mml:mn>0.05</mml:mn></mml:math>). Taken together, our results firstly revealed that high glucose induced the loss of retinal pericytes partly via NLRP3-caspase-1-GSDMD-mediated pyroptosis." @default.
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• W3018968275 date "2020-04-27" @default.
• W3018968275 modified "2023-10-12" @default.
• W3018968275 title "High Glucose Induces the Loss of Retinal Pericytes Partly via NLRP3-Caspase-1-GSDMD-Mediated Pyroptosis" @default.
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• W3018968275 doi "https://doi.org/10.1155/2020/4510628" @default.
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