Integrin and collagen-binding receptor

Cell-surface integrins and collagen-adhesion receptors, including the alpha-v integrin subfamily and discoidin domain receptors (DDR1 and DDR2), are primary mediators of fibroblast interaction with the extracellular matrix (ECM) (Humphries et al., 2019). These receptors are essential for sensing mechanical cues and regulating cell adhesion, migration, and the differentiation of fibroblasts into myofibroblasts during tissue repair (Leask, 2013). In pathological states, their persistent activation drives excessive ECM deposition, leading to organ fibrosis and contributing to the supportive stroma in various cancers (Valiathan et al., 2012). Therapeutic targeting of these receptors aims to interrupt pro-fibrotic signaling, such as the integrin-mediated activation of latent TGF-beta, which is a master regulator of fibrosis (Henderson et al., 2013). While these targets offer significant potential for treating fibroproliferative diseases, their involvement in normal physiological wound healing and tissue maintenance presents a challenge for achieving a favorable therapeutic index (Koivisto et al., 2014).

Other names

Collagen receptorsFibroblast adhesion receptorsCell-matrix adhesion moleculesIntegrin familyDiscoidin domain receptorsCollagen-binding integrins

Inhibition of ligand binding to cell-surface receptors to prevent downstream signaling, reduction of TGF-beta activation, and disruption of fibroblast-to-myofibroblast transition (Henderson et al., 2013; Borradori & Sonnenberg, 1999).