2. Academic Validation
  3. Hypothermic machine perfusion reduces donation after circulatory death liver ischemia-reperfusion injury through the SERPINA3-mediated PI3Kδ/Akt pathway

Hypothermic machine perfusion reduces donation after circulatory death liver ischemia-reperfusion injury through the SERPINA3-mediated PI3Kδ/Akt pathway

  • Hum Cell. 2023 Dec 22. doi: 10.1007/s13577-023-01012-3.
Sheng Peng # 1 2,  Wenjin Liang # 1,  Zhongzhong Liu # 1,  Shaojun Ye 1,  Zhiyong Peng 3,  Zibiao Zhong 4,  Qifa Ye 5 6
Affiliations

Affiliations

  • 1 Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation, Hubei Clinical Research Center for Natural Polymer Biological Liver, Hubei Engineering Center of Natural Polymer-Based Medical Materials, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China.
  • 2 Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
  • 3 Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. [email protected].
  • 4 Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation, Hubei Clinical Research Center for Natural Polymer Biological Liver, Hubei Engineering Center of Natural Polymer-Based Medical Materials, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China. [email protected].
  • 5 Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, National Quality Control Center for Donated Organ Procurement, Hubei Key Laboratory of Medical Technology on Transplantation, Hubei Clinical Research Center for Natural Polymer Biological Liver, Hubei Engineering Center of Natural Polymer-Based Medical Materials, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China. [email protected].
  • 6 Research Center of National Health Ministry on Transplantation Medicine Engineering and Technology, The 3rd Xiangya Hospital of Central South University, Changsha, 410013, China. [email protected].
  • # Contributed equally.
PMID: 38133876 DOI: 10.1007/s13577-023-01012-3
Abstract

Hypothermic machine perfusion (HMP) has been demonstrated to be more effective in mitigating ischemia-reperfusion injury (IRI) of donation after circulatory death (DCD) organs than cold storage (CS), yet the underlying mechanism remains obscure. We aimed to propose a novel therapeutic approach to ameliorate IRI in DCD liver transplantation. Twelve clinical liver samples were randomly assigned to HMP or CS treatment and subsequent transcriptomics analysis was performed. By combining in vivo HMP models, we discovered that HMP attenuated inflammation, oxidative stress, and Apoptosis in DCD liver through a SEPRINA3-mediated PI3Kδ/Akt signaling cascade. Moreover, in the hypoxia/reoxygenation (H/R) model of BRL-3A, overexpression of SERPINA3 mitigated H/R-induced Apoptosis, while SERPINA3 knockdown exacerbated cell injury. Idelalisib (IDE) treatment also reversed the protective effect of SERPINA3 overexpression. Overall, our research provided new insights into therapeutic strategies and identified potential novel molecular targets for therapeutic intervention against DCD liver.

Keywords

Donation after circulatory death; Hypothermic machine perfusion; Ischemia reperfusion injury; PI3kdelta; SERPINA3.

Figures
Products