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HMGB1 in ischemic and non-ischemic liver after selective warm ischemia/reperfusion in rat

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Abstract

High mobility group box 1 (HMGB1) acts as an early mediator in inflammation and organ injury. Ischemia reperfusion (I/R) injury induces HMGB1 translocation and expression in ischemic areas. However, it is unknown whether selective warm liver I/R injury also induces the expression of HMGB1 in non-ischemic lobes. The present study aimed to test the hypothesis that selective liver I/R injury also causes HMGB1 translocation and up-regulates its expression in non-ischemic liver areas. In the present study, selective I/R injury was induced by clamping the median and left lateral liver lobes for 90 min followed by 0.5, 6 and 24 h reperfusion. We used male inbred Lewis rats; six animals for each point in time and six animals for the normal control group. Selective hepatic I/R injury induced morphological changes not only in ischemic lobes but also in non-ischemic lobes. HMGB1 translocation and expression was increased in a time-dependent manner in the ischemic lobes, and increased in with delayed onset in the non-ischemic lobes. Serum HMGB1 levels were increased after reperfusion. Furthermore, liver I/R injury up-regulated the expression of HMGB1 receptors (Toll-like receptor 4 and receptor for advanced glycation end products and pro-inflammatory cytokines (Tumor necrosis factor-alpha and interleukin-6) in both ischemic lobes, however, the up-regulation of these cytokines was more prominent in the ischemic lobes. In conclusion, selective warm I/R induces a substantial “sympathetic/bystander” effect on the non-ischemic lobes in terms of HMGB1 translocation and local cytokine production.

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Acknowledgments

This research was supported partially by the grant “Klinische Forschergruppe 117—Optimierung der Leberlebendspende” (Grant number: Da251/5-3 and 5-4, KFO117). We would like to thank Ms. Tran NgocLan for animal works and Ms. Karin Jandt for linguistic revision. Special thanks go to Prof. Marco E. Bianchi and Prof. Michael T. Lotze for their helpful comments.

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Authors and Affiliations

  1. Experimental Transplantation Surgery, Department of General, Visceral and Vascular Surgery, Friedrich-Schiller-University Jena, Drackendorfer straße1, 07747, Jena, Germany

    Anding Liu, Haoshu Fang, Jian Sun, Hao Jin, Wei Dong & Uta Dahmen

  2. The Centre for Molecular Medicine, Shaoxing People’s Hospital, The First Affiliated Hospital of Shaoxing University, Shaoxing, People’s Republic of China

    Anding Liu

  3. Department of General, Visceral and Transplantation Surgery, University Hospital Essen, University of Duisburg and Essen, Essen, Germany

    Anding Liu, Haoshu Fang, Jian Sun, Hao Jin & Uta Dahmen

  4. Institute for Pathology, University Hospital of Jena, Jena, Germany

    Olaf Dirsch

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  1. Anding Liu
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  2. Olaf Dirsch
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  3. Haoshu Fang
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Correspondence to Uta Dahmen.

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Liu, A., Dirsch, O., Fang, H. et al. HMGB1 in ischemic and non-ischemic liver after selective warm ischemia/reperfusion in rat. Histochem Cell Biol 135, 443–452 (2011). https://doi.org/10.1007/s00418-011-0802-6

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