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Heparin-binding egf-like growth factor contributes to reduced glomerular filtration rate during glomerulonephritis in rats

Academic Article
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Overview

authors

  • Feng, L. L.
  • Garcia, G. E.
  • Yang, Y.
  • Xia, Y. Y.
  • Gabbai, F. B.
  • Peterson, O. W.
  • Abraham, J. A.
  • Blantz, R. C.
  • Wilson, Curtis

publication date

  • February 2000

journal

  • Journal of Clinical Investigation  Journal

abstract

  • Heparin-binding epidermal growth factor-like growth factor (HB-EGF), a member of the epidermal growth factor (EGF) family, is expressed during inflammatory and pathological conditions. We have cloned the rat HB-EGF and followed the expression of HB-EGF in rat kidneys treated with anti- glomerular basement membrane (anti-GBM) antibody (Ab) to induce glomerulonephritis (GN). We observed glomerular HB-EGF mRNA and protein within 30 minutes of Ab administration and showed by in situ hybridization that glomerular HB-EGF mRNA expression was predominantly in mesangial and epithelial cells. Expression of HB-EGF correlated with the onset of decreased renal function in this model. To test the direct effect of HB-EGF on renal function, we infused the renal cortex with active rHB-EGF, prepared from transfected Drosophila melanogaster cells. This treatment induced a significant decrease in single nephron GFR (SNGFR), single nephron plasma flow, and glomerular ultrafiltration coefficient and an increase in the glomerular capillary hydrostatic pressure gradient. In addition, anti-HB-EGF Ab administered just before anti-GBM Ab blocked the fall in SNGFR and GFR at 90 minutes without any change in the glomerular histologic response. These studies suggest that HB-EGF expressed early in the anti-GBM Ab GN model contributes to the observed acute glomerular hemodynamic alterations.

subject areas

  • Animals
  • Epidermal Growth Factor
  • Gene Expression Regulation
  • Gene Transfer Techniques
  • Glomerular Filtration Rate
  • Glomerulonephritis
  • Heparin-binding EGF-like Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • RNA, Messenger
  • Rats
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Identity

International Standard Serial Number (ISSN)

  • 0021-9738

Digital Object Identifier (DOI)

  • 10.1172/jci2869

PubMed ID

  • 10675360
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Additional Document Info

start page

  • 341

end page

  • 350

volume

  • 105

issue

  • 3

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