Inhibiting ATP6V0D2 Aggravates Liver Ischemia-Reperfusion Injury by Promoting NLRP3 Activation via Impairing Autophagic Flux Independent of Notch1/Hes1
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 vacuo...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2021/6670495 |
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| author | Ziyi Wang Hao Wang Xuejiao Chen Sheng Han Yulin Zhu Hanhua Wang Feng Cheng Liyong Pu |
| author_facet | Ziyi Wang Hao Wang Xuejiao Chen Sheng Han Yulin Zhu Hanhua Wang Feng Cheng Liyong Pu |
| author_sort | Ziyi Wang |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c8827e123e154f3689a80ac7b1e1a85c |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-c8827e123e154f3689a80ac7b1e1a85c2025-02-03T01:25:41ZengWileyJournal of Immunology Research2314-88612314-71562021-01-01202110.1155/2021/66704956670495Inhibiting ATP6V0D2 Aggravates Liver Ischemia-Reperfusion Injury by Promoting NLRP3 Activation via Impairing Autophagic Flux Independent of Notch1/Hes1Ziyi Wang0Hao Wang1Xuejiao Chen2Sheng Han3Yulin Zhu4Hanhua Wang5Feng Cheng6Liyong Pu7Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Cardiothoracic Surgery, Affiliated Yancheng Clinical School of Nanjing Medical University, ChinaDepartment of Radiation Oncology, Affiliated Yancheng Clinical School of Nanjing Medical University, ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaAt 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.http://dx.doi.org/10.1155/2021/6670495 |
| spellingShingle | Ziyi Wang Hao Wang Xuejiao Chen Sheng Han Yulin Zhu Hanhua Wang Feng Cheng Liyong Pu Inhibiting ATP6V0D2 Aggravates Liver Ischemia-Reperfusion Injury by Promoting NLRP3 Activation via Impairing Autophagic Flux Independent of Notch1/Hes1 Journal of Immunology Research |
| title | Inhibiting ATP6V0D2 Aggravates Liver Ischemia-Reperfusion Injury by Promoting NLRP3 Activation via Impairing Autophagic Flux Independent of Notch1/Hes1 |
| title_full | Inhibiting ATP6V0D2 Aggravates Liver Ischemia-Reperfusion Injury by Promoting NLRP3 Activation via Impairing Autophagic Flux Independent of Notch1/Hes1 |
| title_fullStr | Inhibiting ATP6V0D2 Aggravates Liver Ischemia-Reperfusion Injury by Promoting NLRP3 Activation via Impairing Autophagic Flux Independent of Notch1/Hes1 |
| title_full_unstemmed | Inhibiting ATP6V0D2 Aggravates Liver Ischemia-Reperfusion Injury by Promoting NLRP3 Activation via Impairing Autophagic Flux Independent of Notch1/Hes1 |
| title_short | Inhibiting ATP6V0D2 Aggravates Liver Ischemia-Reperfusion Injury by Promoting NLRP3 Activation via Impairing Autophagic Flux Independent of Notch1/Hes1 |
| title_sort | inhibiting atp6v0d2 aggravates liver ischemia reperfusion injury by promoting nlrp3 activation via impairing autophagic flux independent of notch1 hes1 |
| url | http://dx.doi.org/10.1155/2021/6670495 |
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