Stretch activates heparin-binding EGF-like growth factor expression in bladder smooth muscle cells

John M. Park, Joseph G. Borer, Michael R. Freeman, Craig A Peters

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Abstract

Cultured rat bladder smooth muscle cells (SMC) were grown on collagen- coated silicone membranes and subjected to continuous cycles of stretch- relaxation. Semiquantitative RT-PCR analysis revealed a time-dependent increase in heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) mRNA levels after stretch, with maximal levels appearing after 4 h. Immunostaining for proHB-EGF revealed higher levels of HB-EGF protein in the stretched than in the nonstretched SMC. The ANG II receptor type 1 antagonist losartan markedly suppressed stretch-activated HB-EGF expression. ANG II levels were 3.3-fold higher in the stretch- than in the non-stretch- conditioned media. Stretch stimulation of bladder SMC that had been transiently transfected with an HB-EGF promoter-luciferase expression construct resulted in an 11-fold increase in reporter activity. Mechanical stretch induced a 4.7-fold increase in tritiated thymidine incorporation rate, and this was reduced by 25% in the presence of losartan. We conclude that mechanical stretch activates HB-EGF gene expression in bladder SMC and that this is mediated in part by autocrine ANG II secretion.

Original languageEnglish (US)
Pages (from-to)C1247-C1254
JournalAmerican Journal of Physiology - Cell Physiology
Volume275
Issue number5 44-5
StatePublished - Dec 5 1998

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Keywords

  • Angiotensin II
  • Bladder outlet obstruction
  • Cell growth
  • Cyclic strain
  • Epidermal growth factor

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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