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High Glucose Induces the Loss of Retinal Pericytes Partly via NLRP3-Caspase-1-GSDMD-Mediated Pyroptosis
Joint Authors
Huang, Maomao
Gan, Jinhua
Lan, Genyin
Liu, Li
Xu, Fangyuan
Source
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-04-27
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
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 (p<0.05) and resulted in the inflammatory cytokines IL-1β and IL-18 and lactate dehydrogenase (LDH) release from HRPs (p<0.05), which are all signs of HRP pyroptosis.
Overexpression of GSDMD facilitated high glucose-induced pyroptosis (all p<0.05).
However, these effects were blunted by synergistically treating DEVD, YVAD, and silencing GSDMD (p<0.05).
Taken together, our results firstly revealed that high glucose induced the loss of retinal pericytes partly via NLRP3-caspase-1-GSDMD-mediated pyroptosis.
American Psychological Association (APA)
Gan, Jinhua& Huang, Maomao& Lan, Genyin& Liu, Li& Xu, Fangyuan. 2020. High Glucose Induces the Loss of Retinal Pericytes Partly via NLRP3-Caspase-1-GSDMD-Mediated Pyroptosis. BioMed Research International،Vol. 2020, no. 2020, pp.1-12.
https://search.emarefa.net/detail/BIM-1133953
Modern Language Association (MLA)
Gan, Jinhua…[et al.]. High Glucose Induces the Loss of Retinal Pericytes Partly via NLRP3-Caspase-1-GSDMD-Mediated Pyroptosis. BioMed Research International No. 2020 (2020), pp.1-12.
https://search.emarefa.net/detail/BIM-1133953
American Medical Association (AMA)
Gan, Jinhua& Huang, Maomao& Lan, Genyin& Liu, Li& Xu, Fangyuan. High Glucose Induces the Loss of Retinal Pericytes Partly via NLRP3-Caspase-1-GSDMD-Mediated Pyroptosis. BioMed Research International. 2020. Vol. 2020, no. 2020, pp.1-12.
https://search.emarefa.net/detail/BIM-1133953
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1133953