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

Research output: Contribution to journalArticle

83 Citations (Scopus)

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)
JournalAmerican Journal of Physiology - Cell Physiology
Volume275
Issue number5 44-5
StatePublished - Dec 5 1998

Fingerprint

Epidermal Growth Factor
Smooth Muscle Myocytes
Muscle
Heparin
Intercellular Signaling Peptides and Proteins
Urinary Bladder
Cells
Losartan
Silicones
Conditioned Culture Medium
Luciferases
Gene expression
Thymidine
Rats
Collagen
Membranes
Gene Expression
Polymerase Chain Reaction
Messenger RNA
Proteins

Keywords

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

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Stretch activates heparin-binding EGF-like growth factor expression in bladder smooth muscle cells. / Park, John M.; Borer, Joseph G.; Freeman, Michael R.; Peters, Craig A.

In: American Journal of Physiology - Cell Physiology, Vol. 275, No. 5 44-5, 05.12.1998.

Research output: Contribution to journalArticle

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