2. Academic Validation
  3. SNX10 promoted liver IR injury by facilitating macrophage M1 polarization via NLRP3 inflammasome activation

SNX10 promoted liver IR injury by facilitating macrophage M1 polarization via NLRP3 inflammasome activation

  • Mol Immunol. 2024 Jan 23:166:79-86. doi: 10.1016/j.molimm.2024.01.009.
Dongming Wu 1,  Yong Wang 2,  Jian Xu 2,  Dong Wang 1,  Jiawei Zhang 1,  Lijuan Meng 3,  Yuanchang Hu 1,  Ping Wang 1,  Jinde Lin 4,  Shun Zhou 5
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 Department of Geriatric Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  • 4 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: [email protected].
  • 5 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: [email protected].
PMID: 38271879 DOI: 10.1016/j.molimm.2024.01.009
Abstract

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.

Keywords

Liver IR injury; Macrophages; Polarization; SNX10; Sterile inflammation.

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