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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Actins / metabolism
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Animals
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Apoptosis*
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Cells, Cultured
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DNA Fragmentation
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DNA Primers / chemistry
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Disease Models, Animal
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Epidermal Growth Factor / genetics
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Epidermal Growth Factor / metabolism*
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Epithelial Cells / metabolism
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Epithelial Cells / pathology
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Female
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Heparin-binding EGF-like Growth Factor
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Humans
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Immunoenzyme Techniques
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Intercellular Signaling Peptides and Proteins
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Keratins / metabolism
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Kidney Cortex / metabolism*
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Kidney Cortex / pathology
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Leucyl Aminopeptidase / metabolism
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Mice
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Muscle, Smooth / metabolism
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Muscle, Smooth / pathology
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RNA, Messenger / metabolism
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Rats
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Rats, Zucker
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Reverse Transcriptase Polymerase Chain Reaction
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Transfection
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Up-Regulation
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Ureteral Obstruction / metabolism*
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Ureteral Obstruction / pathology
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gamma-Glutamyltransferase / metabolism
Substances
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Actins
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DNA Primers
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HBEGF protein, human
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Hbegf protein, mouse
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Hbegf protein, rat
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Heparin-binding EGF-like Growth Factor
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Intercellular Signaling Peptides and Proteins
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RNA, Messenger
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Epidermal Growth Factor
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Keratins
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gamma-Glutamyltransferase
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Leucyl Aminopeptidase