2. Academic Validation
  3. VEGF-C attenuates ischemia reperfusion injury of liver graft in rats

VEGF-C attenuates ischemia reperfusion injury of liver graft in rats

  • Transpl Immunol. 2019 Jun:54:59-64. doi: 10.1016/j.trim.2019.02.004.
Ming-Xiang Cheng 1,  Jin-Zheng Li 1,  Yong Chen 2,  Ding Cao 1,  Jian-Ping Gong 1,  Bing Tu 3
Affiliations

Affiliations

  • 1 Chongqing Key Laboratory of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China; Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 2 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 3 Chongqing Key Laboratory of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China; Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address: 158402084@qq.com.
PMID: 30771456 DOI: 10.1016/j.trim.2019.02.004
Abstract

Background: Vascular endothelial growth factor receptor-3 (VEGFR-3) / vascular endothelial growth factor -c (VEGF-C) signaling is reported to negatively regulate TLR4-triggered inflammation of macrophages. This study aims to clarify whether the VEGFR-3/VEGF-C signaling can suppress Kupffer cells (KCs) activation and attenuate hepatic ischemia-reperfusion injury (IRI) after liver transplantation.

Methods: A rat model of liver transplantation was performed. Donor livers were perfused with VEGF-C injection via portal vein during cold preservation, and controls were perfused with UW solution. Serum levels of alanine transaminase (ALT), total bilirubin (TBIL) and inflammatory cytokines, as well as histology were analyzed after 24 h. KCs were isolated from grafts, RT-PCR and immunofluorescence were used to evaluate polarization-specific marker genes, western bolt was employed to assess the expression of suppressor of cytokine signaling 1(SOCS1) and phosphorylated glycogen synthase kinase 3β (p-GSK3β), and EMSA was utilized to quantify the NF-κB transcriptional activity.

Results: Compared with controls, VEGF-C perfusion reduced ALT and TBIL levels and alleviated liver damage. Furthermore, VEGF-C perfusion suppressed serum proinflammatory cytokines secretion and increased IL-10.In addition, the VEGFR-3 mRNA of KCs was increased after reperfusion. VEGF-C perfusion suppressed NF-κB activity and up-regulated the expression of SOCS1 and p-GSK3β in KCs, and shifted the M1/M2 balance toward an anti-inflammatory profile.

Conclusion: Exogenous VEGF-C protects liver graft from IRI by regulating the inflammatory response and modifying polarization of KCs.

Keywords

Ischemia reperfusion injury; Kupffer cells; Liver transplantation; VEGF-C; VEGFR-3.

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