Ablation of GSDMD Improves Outcome of Ischemic Stroke Through Blocking Canonical and Non-canonical Inflammasomes Dependent Pyroptosis in Microglia

Simple item page
dc.creatorWang, Kankai
dc.creatorSun, Zhezhe
dc.creatorRu, Junnan
dc.creatorWang, Simin
dc.creatorHuang, Lijie
dc.creatorRuan, Linhui
dc.creatorLin, Xiao
dc.creatorJin, Kunlin
dc.creatorZhuge, Qichuan
dc.creatorYang, Su
dc.creator.orcid0000-0002-1336-348X (Jin, Kunlin)
dc.date.accessioned2022-09-09T14:08:38Z
dc.date.available2022-09-09T14:08:38Z
dc.date.issued2020-11-23
dc.description.abstractIschemia/reperfusion (I/R) injury is a significant cause of mortality and long-term disability worldwide. Recent evidence has proved that pyroptosis, a novel cell death form, contributes to inflammation-induced neuron death and neurological function impairment following ischemic stroke. Gasdermin D (GSDMD) is a newly discovered key molecule of cell pyroptosis, but its biological function and precise role in ischemic stroke are still unclear. The present study investigates the cleavage activity of GSDMD, localization of pyroptotic cells, and global neuroinflammation in gsdmd (-/-) mice after I/R. The level of cell pyroptosis around the infarcted area was significantly increased in the acute phase of cerebral I/R injury. The ablation of GSDMD reduced the infraction volume and improved neurological function against cerebral I/R injury. Furthermore, we confirmed I/R injury induced cell pyroptosis mainly in microglia. Knockdown of GSDMD effectively inhibited the secretion of mature IL-1beta and IL-18 from microglia cells but did not affect the expression of caspase-1/11 in vitro and in vivo. In summary, blocking GSDMD expression might serve as a potential therapeutic strategy for ischemic stroke.
dc.description.sponsorshipThis study was financially supported by the National Natural Science Foundation of China (81771262), International (Regional) Cooperation and Exchange Projects of the National Natural Science Foundation of China (81820108011), and Key Project of Science Technology Department of Zhejiang Province (2017C03027 and 2020C03022).
dc.identifier.citationWang, K., Sun, Z., Ru, J., Wang, S., Huang, L., Ruan, L., Lin, X., Jin, K., Zhuge, Q., & Yang, S. (2020). Ablation of GSDMD Improves Outcome of Ischemic Stroke Through Blocking Canonical and Non-canonical Inflammasomes Dependent Pyroptosis in Microglia. Frontiers in neurology, 11, 577927. https://doi.org/10.3389/fneur.2020.577927
dc.identifier.issn1664-2295
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31684
dc.identifier.volume11
dc.publisherFrontiers Media S.A.
dc.relation.urihttps://doi.org/10.3389/fneur.2020.577927
dc.rights.holderCopyright © 2020 Wang, Sun, Ru, Wang, Huang, Ruan, Lin, Jin, Zhuge and Yang.
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceFrontiers in Neurology
dc.subjectgasdermin D
dc.subjectischemia/reperfusion injury
dc.subjectmicroglia
dc.subjectneuroinflammation
dc.subjectneurological outcome
dc.subjectpyroptosis
dc.titleAblation of GSDMD Improves Outcome of Ischemic Stroke Through Blocking Canonical and Non-canonical Inflammasomes Dependent Pyroptosis in Microglia
dc.typeArticle
dc.type.materialtext

Files

Original bundle

Now showing 1 - 1 of 1
Thumbnail Image
Name:
10.3389_fneur.2020.577927.pdf
Size:
2.53 MB
Format:
Adobe Portable Document Format
Description:
full text article
Download

Collections

Publications -- Kunlin Jin