Endothelin-1 promotes mitogenesis in airway smooth muscle cells.

M. K. Glassberg, A. Ergul, A. Wanner, D. Puett

Research output: Contribution to journalArticlepeer-review

99 Scopus citations

Abstract

Endothelin exists as three isoforms (ET-1, ET-2, and ET-3) and exhibits vasoconstricting, bronchoconstricting, and growth-promoting properties in vascular smooth muscle. In the airways, ET-1 immunoreactivity and mRNA have been detected and localized to the epithelium, smooth muscle, and endothelium in different species, including humans. It has been suggested that ET-1 may have a role in the airway smooth muscle hyperplasia and hypertrophy seen in patients with bronchial asthma. We studied ovine airway smooth muscle cells (SMC) in vitro and showed saturable binding of [125I]ET-1 with a dissociation constant (Kd) of 0.4 nM and high affinity binding sites (Bmax) for ET-1 (104 fmol/10(6) cells). This binding was functional as ET-1 promoted mitogenesis of these muscle cells as measured by increased cell number in the absence of serum. Twenty-four hours after exposing the cells to graded doses of ET-1 from 1 pM to 1 microM, cell number increased significantly over control in a dose-dependent manner. ET-1 also enhanced the transient expression of c-fos mRNA by 2.5-fold over control, with maximal expression occurring at 30 min. These observations provide evidence that: (1) airway SMC possess high affinity binding sites for ET-1, and (2) ET-1 is mitogenic for airway SMC as determined by increased cell number and amplification of c-fos mRNA expression. ET-1 may have a fundamental role in influencing the growth of smooth muscle in the airways.

Original languageEnglish (US)
Pages (from-to)316-321
Number of pages6
JournalAmerican journal of respiratory cell and molecular biology
Volume10
Issue number3
DOIs
StatePublished - Mar 1994
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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