title: 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.
abstract: 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.
authors.affiliation: Urologic Laboratory, Department of Urology, Children's Hospital, Boston, MA 02115, USA.
authors.forename: H T
authors.initials: HT
authors.lastname: Nguyen
authors.forename: S H
authors.initials: SH
authors.lastname: Bride
authors.forename: A B
authors.initials: AB
authors.lastname: Badawy
authors.forename: R M
authors.initials: RM
authors.lastname: Adam
authors.forename: J
authors.initials: J
authors.lastname: Lin
authors.forename: A
authors.initials: A
authors.lastname: Orsola
authors.forename: P D
authors.initials: PD
authors.lastname: Guthrie
authors.forename: M R
authors.initials: MR
authors.lastname: Freeman
authors.forename: C A
authors.initials: CA
authors.lastname: Peters
mesh_terms: 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
chemical_list: 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