Home
|
Inbox
|
Search
|
View Abstract
Integrin Alpha2Beta1 Transmits Tension in Smooth Muscle Via Interaction with Collagen and Laminin
Description
.abstract img { width:300px !important; height:auto; display:block; text-align:center; margin-top:10px } .abstract { overflow-x:scroll } .abstract table { width:100%; display:block; border:hidden; border-collapse: collapse; margin-top:10px } .abstract td, th { border-top: 1px solid #ddd; padding: 4px 8px; } .abstract tbody tr:nth-child(even) td { background-color: #efefef; } .abstract a { overflow-wrap: break-word; word-wrap: break-word; }
A2933 - Integrin Alpha2Beta1 Transmits Tension in Smooth Muscle Via Interaction with Collagen and Laminin
Author Block: S. Liu, D. Sheppard, A. B. Sundaram; Lung Biology Center, Department of Medicine, University of California San Francisco, San Francisco, CA, United States.
RATIONALE: Currently available therapeutics target airway smooth muscle by modulating intracellular actin-myosin cross-bridging that contributes to contraction. We have shown that degradation of the extracellular matrix (ECM) protein fibronectin in airway smooth muscle protects against airway contraction by reducing cell-ECM transmission of tension, and furthermore that blockade of integrin α5β1, the primary fibronectin-binding integrin, recapitulates this effect. We sought to determine if other integrins contribute to tension transmission by binding to ECM proteins upregulated in asthma and could thus serve as additional therapeutic targets.
METHODS: qRT-PCR was performed with RNA extracted from human airway smooth muscle (HASM) cells to identify integrins present in smooth muscle, and confirmed with flow cytometry or western blot. Cell adhesion was measured in plates coated with ECM ligands collagen I and laminin I. Tracheal rings from C57/Bl6 wild-type mice were suspended in an organ bath, and after isometric tension was applied, a force transducer measured the dose response to methacholine.
RESULTS: We identified the integrins present in human airway smooth muscle by qRT-PCR and flow cytometry. Of these, those that are highly expressed and thought to bind to laminin I are α3β1 and α6β1; while those that are highly expressed and thought to bind to collagen I are α1β1 and α2β1. Within these candidates, integrin α2β1 contributed significantly to collagen-mediated adhesion, and surprisingly, to laminin-mediated adhesion as well. Blockade of integrin α2β1 in mouse tracheal rings protected against IL-13 enhanced contraction.
CONCLUSIONS: Our data suggest that integrin α2β1 is a major contributor to HASM adhesion to two ECM proteins upregulated in asthma, collagen I and laminin I. Furthermore, our data suggest that blockade of integrin α2β1 protects against cytokine-enhanced bronchoconstriction. Further studies should determine the mechanism of this protection, determine the effect of blockade of integrin α2β1 on in vivo models of allergic asthma, and explore the contraction response after targeting multiple integrin-ECM pathways.
Author Block: S. Liu, D. Sheppard, A. B. Sundaram; Lung Biology Center, Department of Medicine, University of California San Francisco, San Francisco, CA, United States.
RATIONALE: Currently available therapeutics target airway smooth muscle by modulating intracellular actin-myosin cross-bridging that contributes to contraction. We have shown that degradation of the extracellular matrix (ECM) protein fibronectin in airway smooth muscle protects against airway contraction by reducing cell-ECM transmission of tension, and furthermore that blockade of integrin α5β1, the primary fibronectin-binding integrin, recapitulates this effect. We sought to determine if other integrins contribute to tension transmission by binding to ECM proteins upregulated in asthma and could thus serve as additional therapeutic targets.
METHODS: qRT-PCR was performed with RNA extracted from human airway smooth muscle (HASM) cells to identify integrins present in smooth muscle, and confirmed with flow cytometry or western blot. Cell adhesion was measured in plates coated with ECM ligands collagen I and laminin I. Tracheal rings from C57/Bl6 wild-type mice were suspended in an organ bath, and after isometric tension was applied, a force transducer measured the dose response to methacholine.
RESULTS: We identified the integrins present in human airway smooth muscle by qRT-PCR and flow cytometry. Of these, those that are highly expressed and thought to bind to laminin I are α3β1 and α6β1; while those that are highly expressed and thought to bind to collagen I are α1β1 and α2β1. Within these candidates, integrin α2β1 contributed significantly to collagen-mediated adhesion, and surprisingly, to laminin-mediated adhesion as well. Blockade of integrin α2β1 in mouse tracheal rings protected against IL-13 enhanced contraction.
CONCLUSIONS: Our data suggest that integrin α2β1 is a major contributor to HASM adhesion to two ECM proteins upregulated in asthma, collagen I and laminin I. Furthermore, our data suggest that blockade of integrin α2β1 protects against cytokine-enhanced bronchoconstriction. Further studies should determine the mechanism of this protection, determine the effect of blockade of integrin α2β1 on in vivo models of allergic asthma, and explore the contraction response after targeting multiple integrin-ECM pathways.
|
Home
|
Inbox
|
Search
|