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Epidermal growth factor receptor inhibition with erlotinib ameliorates anti-Thy 1.1-induced experimental glomerulonephritis

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Abstract

Background

Mesangial proliferative glomerulonephritis is a common glomerular disorder that may lead to end-stage renal disease. Epidermal growth factor (EGF) plays an important role in the regulation of cell growth, proliferation, and differentiation and in the pathology of various renal diseases. Erlotinib is a novel, oral, highly selective tyrosine kinase inhibitor of the EGF receptor. It is clinically used to treat non-small cell lung and pancreatic cancers. Here, we investigated the effect of erlotinib on the progression of mesangioproliferative glomerulonephritis in an experimental model.

Methods

Mesangial glomerulonephritis was induced with anti-rat Thy-1.1 antibody in male Wistar rats weighing 150–160 g. Rats were treated with erlotinib (10 mg/kg/day p.o.) or vehicle only (polyethylene glycol). Native Wistar rat kidneys were used as histological controls. Serum creatinine levels were measured at day 7. Kidneys were harvested 7 days after antibody administration for histology.

Results

Native controls showed no histological signs of glomerular pathology. In the vehicle group, intense glomerular inflammation developed after 7 days and prominent mesangial cell proliferation and glomerular matrix accumulation was seen. Erlotinib was well tolerated and there were no adverse effects during the follow-up period. Erlotinib significantly prevented progression of the glomerular inflammatory response and glomerular mesangial cell proliferation as well as matrix accumulation when compared with the vehicle group. Erlotinib also preserved renal function.

Conclusion

These results indicate that erlotinib prevents the early events of experimental mesangial proliferative glomerulonephritis. Therefore, inhibition of the EGF receptor with erlotinib could prevent the progression of glomerulonephritis also in clinical nephrology.

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Acknowledgments

This work was supported in part by Finska Läkaresällskapet, the Finnish Medical Foundation, Helsinki University Hospital Research Funds, the Research and Science Foundation of Farmos, Research Funds of Päijät-Häme Central Hospital, and the Academy of Finland.

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Authors and Affiliations

  1. Transplantation Laboratory, University of Helsinki, P.O. Box 21, Haartmaninkatu 3, 00014, Helsinki, Finland

    Jukka M. Rintala, Johanna Savikko, Sini E. Rintala, Niina Palin & Petri K. Koskinen

  2. Transplantation and Liver Surgery Unit, Helsinki University Hospital, Helsinki, Finland

    Johanna Savikko

  3. Division of Nephrology, Department of Medicine, Helsinki University Hospital, Helsinki, Finland

    Petri K. Koskinen

Authors
  1. Jukka M. Rintala
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  2. Johanna Savikko
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  3. Sini E. Rintala
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  4. Niina Palin
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  5. Petri K. Koskinen
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Correspondence to Jukka M. Rintala.

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The authors have no conflicts of interest to disclose.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Rintala, J.M., Savikko, J., Rintala, S.E. et al. Epidermal growth factor receptor inhibition with erlotinib ameliorates anti-Thy 1.1-induced experimental glomerulonephritis. J Nephrol 29, 359–365 (2016). https://doi.org/10.1007/s40620-015-0233-x

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  • DOI: https://doi.org/10.1007/s40620-015-0233-x

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