Endothelin-1 induces increased fibronectin expression in human bronchial epithelial cells.
Endothelin-1 may be involved in the pathogenesis of asthma by causing bronchial smooth muscle constriction and airway remodelling. Bronchial epithelial cells represent an important source of endothelin-1 in this disease, and increased release of epithelial cell-derived endothelin-1 may contribute to the genesis of subepithelial fibrosis by promoting fibroblast proliferation and collagen production. In this study, we demonstrate that endothelin-1 upregulates fibronectin gene expression and fibronectin release in bronchial epithelial cells via an ETA receptor. Fibronectin is an important component of the extracellular matrix which is deposited in excess in the subepithelial area of asthmatic bronchial mucosa, and it represents a potent chemotactic factor for fibroblasts. Thus, endothelin-1 may induce subepithelial fibrosis both directly and by the autocrine mechanism reported here.
Marini
M
M
Institute of Experimental Medicine, Milan, Italy.
Carpi
S
S
Bellini
A
A
Patalano
F
F
Mattoli
S
S
D015152:Blotting, Northern; D001980:Bronchi / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000096:biosynthesis*; D015870:Gene Expression / Q000187:drug effects*; D006020:Glycopeptides / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008175:Lung Neoplasms; D010456:Peptides, Cyclic / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D017466:Receptors, Endothelin / Q000502:physiology; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D005353:Fibronectins; D006020:Glycopeptides; D010456:Peptides, Cyclic; D012333:RNA, Messenger; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6; C072247:cyclo(Trp-Asp-Pro-Val-Leu); C008890:phosphoramidon