Extracellular matrix proteins differentially regulate airway smooth muscle phenotype and function.
Changes in the ECM and increased airway smooth muscle (ASM) mass are major contributors to airway remodeling in asthma and chronic obstructive pulmonary disease. It has recently been demonstrated that ECM proteins may differentially affect proliferation and expression of phenotypic markers of cultured ASM cells. In the present study, we investigated the functional relevance of ECM proteins in the modulation of ASM contractility using bovine tracheal smooth muscle (BTSM) preparations. The results demonstrate that culturing of BSTM strips for 4 days in the presence of fibronectin or collagen I depressed maximal contraction (E(max)) both for methacholine and KCl, which was associated with decreased contractile protein expression. By contrast, both fibronectin and collagen I increased proliferation of cultured BTSM cells. Similar effects were observed for PDGF. Moreover, PDGF augmented fibronectin- and collagen I-induced proliferation in an additive fashion, without an additional effect on contractility or contractile protein expression. The fibronectin-induced depression of contractility was blocked by the integrin antagonist Arg-Gly-Asp-Ser (RGDS) but not by its negative control Gly-Arg-Ala-Asp-Ser-Pro (GRADSP). Laminin, by itself, did not affect contractility or proliferation but reduced the effects of PDGF on these parameters. Strong relationships were found between the ECM-induced changes in E(max) in BTSM strips and their proliferative responses in BSTM cells and for E(max) and contractile protein expression. Our results indicate that ECM proteins differentially regulate both phenotype and function of intact ASM.
Dekkers
Bart G J
BG
Department of Molecular Pharmacology, University Centre for Pharmacy, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands. B.G.J.Dekkers@rug.nl
Schaafsma
Dedmer
D
Nelemans
S Adriaan
SA
Zaagsma
Johan
J
Meurs
Herman
H
D000818:Animals; D016085:Bronchoconstrictor Agents / Q000494:pharmacology; D002417:Cattle; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D024042:Collagen Type I / Q000378:metabolism / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000378:metabolism* / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism* / Q000494:pharmacology; D007797:Laminin / Q000378:metabolism / Q000494:pharmacology; D016210:Methacholine Chloride / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000166:cytology / Q000502:physiology*; D009924:Organ Culture Techniques; D010641:Phenotype; D011189:Potassium Chloride / Q000494:pharmacology; D014132:Trachea / Q000166:cytology / Q000502:physiology*
D016085:Bronchoconstrictor Agents; D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D007797:Laminin; D016210:Methacholine Chloride; D011189:Potassium Chloride