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Role of hepatic stellate cells on graft injury after small-for-size liver transplantation

Authors

  • Wei Chen,

    1. Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation of Ministry of Public Health, Key Laboratory of Organ Transplantation of Zhejiang Province, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, China
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  • Liang Liang,

    1. Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation of Ministry of Public Health, Key Laboratory of Organ Transplantation of Zhejiang Province, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, China
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  • Tao Ma,

    1. Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation of Ministry of Public Health, Key Laboratory of Organ Transplantation of Zhejiang Province, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, China
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  • Junjian Li,

    1. Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation of Ministry of Public Health, Key Laboratory of Organ Transplantation of Zhejiang Province, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, China
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  • Guodong Xu,

    1. Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation of Ministry of Public Health, Key Laboratory of Organ Transplantation of Zhejiang Province, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, China
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  • Yun Zhang,

    1. Emergency Medicine, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
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  • Xueli Bai,

    1. Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation of Ministry of Public Health, Key Laboratory of Organ Transplantation of Zhejiang Province, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, China
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  • Tingbo Liang

    Corresponding author
    1. Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-organ Transplantation of Ministry of Public Health, Key Laboratory of Organ Transplantation of Zhejiang Province, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, China
      Professor Tingbo Liang, Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-Organ Transplantation of Ministry of Public Health, Key Laboratory of Organ Transplantation of Zhejiang Province, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, the First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China. Email: liangtingbo@zju.edu.cn
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Professor Tingbo Liang, Department of Hepatobiliary and Pancreatic Surgery, Key Laboratory of Combined Multi-Organ Transplantation of Ministry of Public Health, Key Laboratory of Organ Transplantation of Zhejiang Province, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, the First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China. Email: liangtingbo@zju.edu.cn

Abstract

Background and Aim:  Small-for-size grafts are prone to mechanical injury and a series of chemical injuries that are related to hemodynamic force. Hepatic stellate cells activate and trans-differentiate into contractile myofibroblast-like cells during liver injury. However, the role of hepatic stellate cells on sinusoidal microcirculation is unknown with small-for-size grafts.

Methods:  Thirty-five percent of small-for-size liver transplantation was performed with rats as donors and recipients. Endothelin-1 levels as well as hepatic stellate cells activation-related protein expression, endothelin-1 receptors, and ultrastructural changes were examined. The cellular localizations of two types of endothelin-1 receptors were detected. Furthermore, liver function and sinusoidal microcirculation were analyzed using two different selective antagonists of endothelin-1 receptor.

Results:  Intragraft expression of hepatic stellate cells activation-related protein such as desmin, crystallin-B and smooth muscle α-actin was upregulated as well as serum endothelin-1 levels and intragraft expression of the two endothelin receptors. The antagonist to endothelin-1 A receptor not to the endothelin-1 B receptor could attenuate microcirculatory disturbance and improve liver function.

Conclusions:  Small-for-size liver transplantation displayed increased hepatic stellate cells activation and high level of endothelin-1 binding to upregulation of endothelin-1 A receptor on hepatic stellate cells, which contracted hepatic sinusoid inducing graft injury manifested as reduction of sinusoidal perfusion rate and elevation of sinusoidal blood flow.

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