Heparin-binding EGF-like growth factor is up-regulated in the obstructed kidney in a cell- and region-specific manner and acts to inhibit apoptosis

The expression of certain growth factors in the epidermal growth factor (EG F) family is altered in response to renal injury. Recent studies have demon strated that heparin binding EGF-like growth factor (HB-EGF) expression may be cytoprotective in response to apoptotic signals. The purpose of this st udy was to investigate the potential role of HB-EGF in the upper urinary tr act following unilateral ureteral obstruction. We present evidence that: i) ureteral obstruction induced cell-specific but transient activation of HB- EGF gene expression; ii) HB-EGF expression in renal epithelial cells increa sed under conditions where mechanical deformation, such as that caused by h ydronephrotic distension, induces apoptosis,but HB-EGF expression did not i ncrease in renal pelvis smooth muscle cells under identical conditions; and iii) enforced expression of HB-EGF served to protect renal epithelial cell s from stretch-induced apoptosis. These results suggest a potential mechani sm by which the kidney protects itself from apoptosis triggered by urinary tract obstruction.