Type I Collagen Signaling Regulates Opposing Fibrotic Pathways through Alpha2Beta1 Integrin.

Type I Collagen Signaling Regulates Opposing Fibrotic Pathways through Alpha2Beta1 Integrin. Am J Respir Cell Mol Biol. 2020 Jul 21;: Authors: Agarwal M, Goheen M, Jia S, Ling S, White ES, Kim KK Abstract Fibrosis is characterized by fibroblast activation, leading to matrix remodeling culminating in a stiff, type I collagen rich fibrotic matrix. Alveolar epithelial cell (AEC) apoptosis is also a major feature of fibrogenesis and AEC apoptosis is sufficient to initiate a robust lung fibrotic response. TGFβ is a major driver of fibrosis and can induced both AEC apoptosis and fibroblast activation. We and others have previously shown that changes in extracellular matrix stiffness and composition can regulate the cellular response to TGFβ. In the present study we find that type I collagen signaling promotes TGFβ mediated fibroblast activation and inhibits TGFβ-induced AEC death. Fibroblasts cultured on type I collagen or fibrotic decellularized lung matrix had augmented activation in response to TGFβ while AECs on cultured on type I collagen or fibrotic lung matrix were more resistant to TGFβ-induced apoptosis. Both of these responses were mediated by integrin α2β1, a major collagen receptor. AECs treated with an α2 integrin inhibitor or with deletion of α2 integrin had loss of collagen-mediated protection from apoptosis. We found that mice with fibroblast specific deletion of α2 integrin were protected from fibrosis while mic...
Source: Mol Biol Cell - Category: Molecular Biology Authors: Tags: Am J Respir Cell Mol Biol Source Type: research