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Inhibiting ATP6V0D2 Aggravates Liver Ischemia-Reperfusion Injury by Promoting NLRP3 Activation via Impairing Autophagic Flux Independent of Notch1/Hes1

Authors :
Ziyi Wang
Hao Wang
Xuejiao Chen
Sheng Han
Yulin Zhu
Hanhua Wang
Feng Cheng
Liyong Pu
Source :
Journal of Immunology Research, Vol 2021 (2021)
Publication Year :
2021
Publisher :
Hindawi Limited, 2021.

Abstract

At present, liver ischemia-reperfusion (IR) injury is still a great challenge for clinical liver partial resection and liver transplantation. The innate immunity regulated by liver macrophages orchestrates the cascade of IR inflammation and acts as a bridge. As a specific macrophage subunit of vacuolar ATPase, ATP6V0D2 (V-ATPase D2 subunit) has been shown to promote the formation of autophagolysosome in vitro. Our research fills a gap which has existed in the study of inflammatory stress about the V-ATPase subunit ATP6V0D2 in liver macrophages. We first found that the expression of specific ATP6V0D2 in liver macrophages was upregulated with the induction of inflammatory cascade after liver IR surgery, and knockdown of ATP6V0D2 resulted in increased secretion of proinflammatory factors and chemokines, which enhanced activation of NLRP3 and aggravation of liver injury. Further studies found that the exacerbated activation of NLRP3 was related to the autophagic flux regulated by ATP6V0D2. Knocking down ATP6V0D2 impaired the formation of autophagolysosome and aggravated liver IR injury through nonspecific V-ATPase activation independent of V-ATPase-Notchl-Hesl signal axis. In general, we illustrated that the expression of ATP6V0D2 in liver macrophages was upregulated after liver IR, and by gradually promoting the formation of autophagolysosomes to increase autophagy flux to limit the activation of liver inflammation, this regulation is independent of the Notch1-Hes1 signal axis.

Details

Language :
English
ISSN :
23148861 and 23147156
Volume :
2021
Database :
Directory of Open Access Journals
Journal :
Journal of Immunology Research
Publication Type :
Academic Journal
Accession number :
edsdoj.8827e123e154f3689a80ac7b1e1a85c
Document Type :
article
Full Text :
https://doi.org/10.1155/2021/6670495