Endothelin-1 promotes mitogenesis in airway smooth muscle cells.
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.
Glassberg
M K
MK
Department of Medicine, University of Miami School of Medicine, FL 33101.
Ergul
A
A
Wanner
A
A
Puett
D
D
D000818:Animals; D001665:Binding Sites; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016232:Endothelins / Q000378:metabolism / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos; D008934:Mitogens / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012756:Sheep; D013194:Staining and Labeling; D014132:Trachea / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism
D016232:Endothelins; D008934:Mitogens; D012333:RNA, Messenger