Matrix Hyaluronan-Activated CD44 Signaling Promotes Keratinocyte Activities and Improves Abnormal Epidermal Functions

摘要: Hyaluronan (HA), a major component of the extracellular matrix, is enriched in skin tissues, particularly epidermis. HA binds to ubiquitous, abundant, and functionally important family cell surface receptors, CD44. This article reviews current evidence for HA/CD44-mediated activation RhoGTPase signaling calcium mobilization, leading regulation keratinocyte activities various epidermal functions. It further discusses role HA-mediated CD44 interactions with unique downstream effectors, such as RhoGTPases (RhoA Rac1), Rho-kinase, protein kinase-Nγ, phosphoinositide-specific phospholipases (phospholipases Ce Cγ1) coordinating certain intracellular pathways, phosphatidylinositol 3-kinase–AKT activation, cortactin-actin binding, actin-associated cytoskeleton reorganization; generating onset activities, adhesion, proliferation, migration, differentiation; performing Topical application selective fragments (large versus small HA) wild-type mice (but not knockout mice) improves keratinocyte-associated functions accelerates permeability barrier recovery wound healing. Consequently, specific fragment HA)–mediated events (through receptor) are required which offer new HA-based therapeutic options patients experiencing dysfunction damage well aging-related diseases, thinning (atrophy), dysfunction, chronic nonhealing wounds.