PMID- 38271879
OWN - NLM
STAT- MEDLINE
DCOM- 20240214
LR  - 20240214
IS  - 1872-9142 (Electronic)
IS  - 0161-5890 (Linking)
VI  - 166
DP  - 2024 Feb
TI  - SNX10 promoted liver IR injury by facilitating macrophage M1 polarization via 
      NLRP3 inflammasome activation.
PG  - 79-86
LID - S0161-5890(24)00017-8 [pii]
LID - 10.1016/j.molimm.2024.01.009 [doi]
AB  - BACKGROUND: Liver ischemia reperfusion (IR) injury is a common cause of liver 
      dysfunction in patients post liver partial resection and liver transplantation. 
      However, the cellular defense mechanisms underlying IR are not well understood. 
      Macrophage mediated sterile inflammation plays critical roles in liver IR injury. 
      Sorting nexin (SNX) 10, a member of the SNX family which functions in regulation 
      of endosomal sorting. This study aimed to explore the role of sorting nexin 10 
      (SNX10) during liver IR injury with a focus on regulating macrophage function. 
      METHODS: Both the gene and protein expression levels of SNX10 were analyzed in 
      human specimens from 10 patients undergoing liver partial resection with ischemic 
      insult and in a mouse model of liver IR. The in vivo effects of SNX10 in liver IR 
      injury and sterile inflammation in mice were investigated. Bone marrow derived 
      macrophages (BMDMs) were used to determine the role of SNX10 in modulating 
      macrophage function in vitro. RESULTS: Increased expression of SNX10 was observed 
      both in human specimens and mice livers post IR. SNX10 knockdown alleviated IR 
      induced sterile inflammation and liver damage in mice. SNX10 promoted M1 
      polarization of macrophage treated with LPS and facilitated inflammatory response 
      by activating NLRP3 inflammasome. CONCLUSIONS: We report for the first time that 
      SNX10 is upregulated in IR-stressed livers. SNX10 activation aggravates liver IR 
      injury and sterile inflammation by facilitating macrophage M1 polarization and 
      inflammatory response suggesting SNX10 as a potential therapeutic target for 
      liver IR injury.
CI  - Copyright (c) 2024. Published by Elsevier Ltd.
FAU - Wu, Dongming
AU  - Wu D
AD  - Department of Plastic and Cosmetic Surgery of The Affiliated Friendship Plastic 
      Surgery Hospital & Hepatobiliary Center of The First Affiliated Hospital, Nanjing 
      Medical University, Nanjing, China; NHC Key Laboratory of Living Donor Liver 
      Transplantation (Nanjing Medical University), Nanjing, China; Key Laboratory of 
      Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China.
FAU - Wang, Yong
AU  - Wang Y
AD  - Department of Plastic and Cosmetic Surgery of The Affiliated Friendship Plastic 
      Surgery Hospital & Hepatobiliary Center of The First Affiliated Hospital, Nanjing 
      Medical University, Nanjing, China.
FAU - Xu, Jian
AU  - Xu J
AD  - Department of Plastic and Cosmetic Surgery of The Affiliated Friendship Plastic 
      Surgery Hospital & Hepatobiliary Center of The First Affiliated Hospital, Nanjing 
      Medical University, Nanjing, China.
FAU - Wang, Dong
AU  - Wang D
AD  - Department of Plastic and Cosmetic Surgery of The Affiliated Friendship Plastic 
      Surgery Hospital & Hepatobiliary Center of The First Affiliated Hospital, Nanjing 
      Medical University, Nanjing, China; NHC Key Laboratory of Living Donor Liver 
      Transplantation (Nanjing Medical University), Nanjing, China; Key Laboratory of 
      Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China.
FAU - Zhang, Jiawei
AU  - Zhang J
AD  - Department of Plastic and Cosmetic Surgery of The Affiliated Friendship Plastic 
      Surgery Hospital & Hepatobiliary Center of The First Affiliated Hospital, Nanjing 
      Medical University, Nanjing, China; NHC Key Laboratory of Living Donor Liver 
      Transplantation (Nanjing Medical University), Nanjing, China; Key Laboratory of 
      Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China.
FAU - Meng, Lijuan
AU  - Meng L
AD  - Department of Geriatric Oncology, The First Affiliated Hospital of Nanjing 
      Medical University, Nanjing, China.
FAU - Hu, Yuanchang
AU  - Hu Y
AD  - Department of Plastic and Cosmetic Surgery of The Affiliated Friendship Plastic 
      Surgery Hospital & Hepatobiliary Center of The First Affiliated Hospital, Nanjing 
      Medical University, Nanjing, China; NHC Key Laboratory of Living Donor Liver 
      Transplantation (Nanjing Medical University), Nanjing, China; Key Laboratory of 
      Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China.
FAU - Wang, Ping
AU  - Wang P
AD  - Department of Plastic and Cosmetic Surgery of The Affiliated Friendship Plastic 
      Surgery Hospital & Hepatobiliary Center of The First Affiliated Hospital, Nanjing 
      Medical University, Nanjing, China; NHC Key Laboratory of Living Donor Liver 
      Transplantation (Nanjing Medical University), Nanjing, China; Key Laboratory of 
      Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China.
FAU - Lin, Jinde
AU  - Lin J
AD  - Department of Plastic and Cosmetic Surgery of The Affiliated Friendship Plastic 
      Surgery Hospital & Hepatobiliary Center of The First Affiliated Hospital, Nanjing 
      Medical University, Nanjing, China. Electronic address: hzljd@sohu.com.
FAU - Zhou, Shun
AU  - Zhou S
AD  - Department of Plastic and Cosmetic Surgery of The Affiliated Friendship Plastic 
      Surgery Hospital & Hepatobiliary Center of The First Affiliated Hospital, Nanjing 
      Medical University, Nanjing, China; NHC Key Laboratory of Living Donor Liver 
      Transplantation (Nanjing Medical University), Nanjing, China; Key Laboratory of 
      Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China. 
      Electronic address: hand2399@njmu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20240124
PL  - England
TA  - Mol Immunol
JT  - Molecular immunology
JID - 7905289
RN  - 0 (Inflammasomes)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Sorting Nexins)
RN  - 0 (SNX10 protein, human)
RN  - 0 (SNX10 protein, mouse)
SB  - IM
MH  - Humans
MH  - Animals
MH  - Mice
MH  - *Inflammasomes/metabolism
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
MH  - Sorting Nexins/genetics/metabolism
MH  - Liver/metabolism
MH  - Macrophages/metabolism
MH  - Inflammation/metabolism
MH  - *Reperfusion Injury/metabolism
OTO - NOTNLM
OT  - Liver IR injury
OT  - Macrophages
OT  - Polarization
OT  - SNX10
OT  - Sterile inflammation
COIS- Declaration of Competing Interest The authors have no conflicts of interest to 
      declare.
EDAT- 2024/01/26 00:44
MHDA- 2024/02/11 16:42
CRDT- 2024/01/25 18:08
PHST- 2023/09/10 00:00 [received]
PHST- 2023/12/26 00:00 [revised]
PHST- 2024/01/17 00:00 [accepted]
PHST- 2024/02/11 16:42 [medline]
PHST- 2024/01/26 00:44 [pubmed]
PHST- 2024/01/25 18:08 [entrez]
AID - S0161-5890(24)00017-8 [pii]
AID - 10.1016/j.molimm.2024.01.009 [doi]
PST - ppublish
SO  - Mol Immunol. 2024 Feb;166:79-86. doi: 10.1016/j.molimm.2024.01.009. Epub 2024 Jan 
      24.