1. Heparin binding epidermal growth factor in renal ischaemia/reperfusion injury
- Author
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Mulder, GM, Nijboer, WN, Seelen, MA, Sandovici, M, Bos, EM, Melenhorst, WB, Trzpis, M, Kloosterhuis, NJ, Visser, L, Henning, RH, Leuvenink, HG, Ploeg, RJ, Sunnarborg, SW, van Goor, H, Groningen Institute for Organ Transplantation (GIOT), Groningen Kidney Center (GKC), Stem Cell Aging Leukemia and Lymphoma (SALL), Vascular Ageing Programme (VAP), and Translational Immunology Groningen (TRIGR)
- Subjects
urogenital system ,proliferation ,fibrosis ,EARLY PHASE ,FACTOR-ALPHA ,human biopsies ,renal transplantation ,urologic and male genital diseases ,FACTOR MESSENGER-RNA ,ISCHEMIA/REPERFUSION INJURY ,MICE LACKING ,PKI-166 ,RAT-KIDNEY ,HB-EGF ,ANGIOTENSIN-II ,EGF receptor ,MESANGIAL CELLS ,cardiovascular diseases ,ischaemia/reperfusion injury ,FACTOR RECEPTOR INHIBITION ,hormones, hormone substitutes, and hormone antagonists - Abstract
The epidermal growth factor (EGF) receptor and its ligands are crucially involved in the renal response to ischaemia. We studied the heparin binding-epidermal growth factor (HB-EGF), a major ligand for the EGF receptor, in experimental and human ischaemia/reperfusion injury (IRI). HB-EGF mRNA and protein expression was studied in rat kidneys and cultured human tubular (HK-2) cells that were subjected to IRI and in human donor kidneys during transplantation. The effect of EGF receptor inhibition was investigated in vivo and in vitro. Furthermore, urinary HB-EGF protein excretion was studied after renal transplantation. Finally, HB-EGF KO and WT mice were subjected to IRI to study the role of HB-EGF in renal injury. HB-EGF mRNA was significantly up-regulated in the early phase of IRI in rats, cells, and human donor biopsies. Treatment with PKI-166 reduces macrophage accumulation and interstitial alpha-SMA in the early phase of IRI in rats. In vitro, PKI-166 causes a marked reduction in HB-EGF-induced cellular proliferation. Urinary HB-EGF is increased after transplantation compared with control urines from healthy subjects. HB-EGF KO mice subjected to IRI revealed significantly less morphological damage after IRI, compared with WT mice. We conclude that IRI results in early induction of HB-EGF mRNA and protein in vivo and in vitro. Absence of HB-EGF and inhibition of the EGF receptor in the early phase of IRI has protective effects, suggesting a modulating role for HB-EGF. Copyright (C) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
- Published
- 2016