Increased expression of HB-EGF and its receptor erbB4/HER4 in accelerated anti-GBM disease.

SUMMARY: In the kidney, heparin-binding epidermal growth factor-like growth factor (HB-EGF) and its receptors, epidermal growth factor–receptor (EGF-R) and human epidermal receptor 4 (erbB4/ HER4), may be important in the response of cells to tissue injury. To further define the role of HB-EGF, we have determined its distribution in the accelerated anti-GBM model of kidney disease. Within the glomerulus, immunohistochemical staining showed increased HB-EGF expression in podocytes and infiltrating macrophages. This was associated with strong de novo expression of erbB4/HER4 on podocytes. These data suggest that increased expression of HB-EGF and erbB4/HER4 is a response to inflammation in the glomerulus in accelerated anti-GBM disease. To determine the potential role of HB-EGF in anti-GBM disease, a blocking monoclonal antibody against HB-EGF (DE10) was administered by intravenous injection. There was, however, no significant difference in the extent of 24 h urinary protein, renal function, or histological appearances. The effects of blocking HB-EGF, therefore, may be masked by the redundancy in the EGF growth factor family. [ABSTRACT FROM AUTHOR]