Upregulation of heparin-binding epidermal growth factor-like growth factor and osteopontin in experimental hydronephrosis

SUMMARY This study examined the expression of heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF) and osteopontin in unilateral ureteral obstruction (UUO) in the rat, a model of obstructive uropathy. HB‐EGF mRNA was upregulated 5.5‐fold at 4 h post‐obstruction (P < 0.05) and 4.5‐f...

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Bibliographic Details
Published in:	Nephrology (Carlton, Vic.) Vol. 5; no. 3; pp. 201 - 208
Main Authors:	Katerelos, M, Kirkland, G, Paizis, K, Khong, T, KANELLIS1, J., Power, Da
Format:	Journal Article
Language:	English
Published:	Melbourne, Australia Blackwell Science Pty 01-10-2000
Subjects:	heparin-binding epidermal growth factor-like growth factor interstitial fibrosis myofibroblast transformation unilateral ureteral obstruction
Online Access:	Get full text
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Summary:	SUMMARY This study examined the expression of heparin‐binding epidermal growth factor‐like growth factor (HB‐EGF) and osteopontin in unilateral ureteral obstruction (UUO) in the rat, a model of obstructive uropathy. HB‐EGF mRNA was upregulated 5.5‐fold at 4 h post‐obstruction (P < 0.05) and 4.5‐fold after 12 h (P < 0.05). Immunohistochemical staining for HB‐EGF demonstrated an increase in protein in the distended tubules. To determine what effects increased HB‐EGF might have in the obstructed kidney, we attempted to determine whether HB‐EGF upregulates osteopontin and α‐smooth muscle actin (α‐SMA) in the tubular line NRK‐52E. Both of these molecules are increased in UUO. Osteopontin mRNA was upregulated in NRK‐52E cells after 24, 48 and 72 h HB‐EGF stimulation. In contrast, HB‐EGF caused a downregulation of α‐SMA protein by Western blot in NRK‐52E cells. When a blocking mAb against secreted HB‐EGF was administered, however, there was no effect on osteopontin mRNA levels or immunohistochemical staining for α‐smooth muscle actin. These data suggest that the action of HB‐EGF in UUO may be to increase osteopontin and reduce α‐smooth muscle actin expression by tubular epithelial cells by an autocrine or intracrine mechanism. By reducing α‐SMA expression, HB‐EGF may also act to maintain epithelial cell morphology in this model.
Bibliography:	istex:676BA9356D168441CD521AF3FA0A6023EF21F0DB ark:/67375/WNG-KVWPPX35-X ArticleID:NEP5 † Department of Medicine, Renal Unit, Flinders Medical Center, Bedford Park, South Australia 5042, Australia. Present addresses: *Department of Nephrology, Royal Hobart Hospital, Hobart, Tasmania 7000, Australia and
ISSN:	1320-5358 1440-1797
DOI:	10.1046/j.1440-1797.2000.00005.x