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

Marina Katerelos, G. Kirkl, Kathy Paizis, T. Khong, J. Kanellis, Da Power

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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 12h (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.

Original languageEnglish
Pages (from-to)201-208
Number of pages8
JournalNephrology
Volume5
Issue number3
DOIs
Publication statusPublished - 2000
Externally publishedYes

Keywords

  • Heparin-binding epidermal growth factor-like growth factor
  • Interstitial fibrosis
  • Myofibroblast transformation
  • Unilateral ureteral obstruction

Cite this

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title = "Upregulation of heparin-binding epidermal growth factor-like growth factor and osteopontin in experimental hydronephrosis",
abstract = "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 12h (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.",
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author = "Marina Katerelos and G. Kirkl and Kathy Paizis and T. Khong and J. Kanellis and Da Power",
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Upregulation of heparin-binding epidermal growth factor-like growth factor and osteopontin in experimental hydronephrosis. / Katerelos, Marina; Kirkl, G.; Paizis, Kathy; Khong, T.; Kanellis, J.; Power, Da.

In: Nephrology, Vol. 5, No. 3, 2000, p. 201-208.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Upregulation of heparin-binding epidermal growth factor-like growth factor and osteopontin in experimental hydronephrosis

AU - Katerelos, Marina

AU - Kirkl, G.

AU - Paizis, Kathy

AU - Khong, T.

AU - Kanellis, J.

AU - Power, Da

PY - 2000

Y1 - 2000

N2 - 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 12h (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.

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KW - Heparin-binding epidermal growth factor-like growth factor

KW - Interstitial fibrosis

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DO - 10.1046/j.1440-1797.2000.00005.x

M3 - Article

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EP - 208

JO - Nephrology

JF - Nephrology

SN - 1320-5358

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