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 (EGF) family is altered in response to renal injury. Recent studies have demonstrated that heparin binding EGF-like growth factor (HB-EGF) expression may be cytoprotective in response to apoptotic signals. The purpose of this study was to investigate the potential role of HB-EGF in the upper urinary tract 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 increased under conditions where mechanical deformation, such as that caused by hydronephrotic distension, induces apoptosis, but HB-EGF expression did not increase in renal pelvis smooth muscle cells under identical conditions; and iii) enforced expression of HB-EGF served to protect renal epithelial cells from stretch-induced apoptosis. These results suggest a potential mechanism by which the kidney protects itself from apoptosis triggered by urinary tract obstruction.
Nguyen
H T
HT
Urologic Laboratory, Department of Urology, Children's Hospital, Boston, MA 02115, USA.
Bride
S H
SH
Badawy
A B
AB
Adam
R M
RM
Lin
J
J
Orsola
A
A
Guthrie
P D
PD
Freeman
M R
MR
Peters
C A
CA
D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D053938:DNA Fragmentation; D017931:DNA Primers / Q000737:chemistry; D004195:Disease Models, Animal; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D007124:Immunoenzyme Techniques; D036341:Intercellular Signaling Peptides and Proteins; D007633:Keratins / Q000378:metabolism; D007672:Kidney Cortex / Q000378:metabolism* / Q000473:pathology; D007931:Leucyl Aminopeptidase / Q000378:metabolism; D051379:Mice; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D015854:Up-Regulation; D014517:Ureteral Obstruction / Q000378:metabolism* / Q000473:pathology; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D000199:Actins; D017931:DNA Primers; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; C587885:Hbegf protein, rat; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D004815:Epidermal Growth Factor; D007633:Keratins; D005723:gamma-Glutamyltransferase; D007931:Leucyl Aminopeptidase