Hyaluronan receptors and extracellular matrix

The physiological extracellular matrix (ECM) and endogenous hyaluronic acid (HA) receptors represent a complex structural and signaling network essential for tissue integrity and cellular communication (Laurent & Fraser, 1992, PubMed: 1533750). HA, a major glycosaminoglycan component of the ECM, interacts non-selectively with various receptors, most notably CD44, RHAMM, and LYVE-1, to regulate processes such as cell proliferation, migration, and inflammation (Vigetti et al., 2014, PubMed: 24303333). In therapeutic contexts, particularly in orthopedics and dermatology, this target is addressed through the administration of exogenous HA or its derivatives (FDA P900060). These treatments aim to restore the mechanical properties of the ECM, provide lubrication in joints, and modulate cellular signaling pathways through receptor interaction (Turley et al., 2002, PubMed: 12130512). Dysregulation of this system is implicated in diseases like osteoarthritis, where HA concentration decreases, and in cancer, where HA-receptor interactions promote tumor progression and metastasis (Misra et al., 2011, PubMed: 21637761). Consequently, targeting this interaction serves both structural and pharmacological purposes in clinical medicine. The non-selective nature of these interactions means that exogenous HA can influence multiple pathways simultaneously, providing a broad therapeutic effect. This target is unique because it encompasses both a physical scaffold and a set of biochemical signaling receptors.

Other names

Physiological extracellular matrix and endogenous hyaluronic acid receptors – non-selective physiological interactionECM-HA receptor complexHyaladherinsHyaluronan-binding proteinsHyaluronan-receptor system

Exogenous hyaluronan derivatives act by physically augmenting the extracellular matrix and binding non-selectively to endogenous receptors like CD44 to modulate inflammatory signaling and provide mechanical lubrication.