Elastin receptor complex (ERC)

The term 'Fibroblast cell-surface receptors for matrikines' primarily refers to the Elastin Receptor Complex (ERC) and certain integrins (e.g., alpha-v beta-3) that mediate the biological effects of extracellular matrix fragments (Scandolera et al., 2016; ersnet.org). The ERC is a heterotrimeric complex consisting of the 67-kDa elastin-binding protein (EBP), neuraminidase-1 (Neu-1), and protective protein/cathepsin A (PPCA) (Duca et al., 2007). Activation of these receptors by matrikines, such as elastin-derived peptides (EDPs) or collagen fragments, triggers signaling pathways including ERK1/2, PI3K/Akt, and FAK (Rusciani et al., 2010; Maquart et al., 1999). These pathways regulate fibroblast proliferation, migration, and matrix metalloproteinase expression, which are critical for physiological wound healing (Maquart et al., 1999). However, these interactions become dysregulated in pathological states like idiopathic pulmonary fibrosis, atherosclerosis, and cancer, where they promote excessive remodeling and tumor progression (Scandolera et al., 2016). In aging, the ERC becomes uncoupled, contributing to the loss of fibroblast function and skin elasticity (Scandolera et al., 2016). Therapeutic strategies include the use of competitive peptides like V14, Neu-1 inhibitors such as oseltamivir, and integrin antagonists like cilengitide to disrupt these pro-pathogenic signaling loops (Scandolera et al., 2016; ersnet.org). Additionally, galactosugars like lactose can be used to dissociate the ERC and inhibit its signaling (Mecham et al., 1991).

Other names

Matrikine receptorEBP-Neu1-PPCA complex67-kDa elastin/laminin binding proteinFibroblast matrikine receptorFibroblast cell-surface receptors for matrikines

Matrikine binding to the ERC triggers Neu1-mediated desialylation of gangliosides to produce lactosylceramide, while binding to integrins activates FAK/PI3K signaling, both leading to ERK1/2 activation and downstream gene expression (Scandolera et al., 2016; Rusciani et al., 2010; ersnet.org).