HAreceptor

HA receptor is a term used to describe receptors that bind hyaluronic acid (HA), a large, non-sulfated glycosaminoglycan present in the extracellular matrix and on cell surfaces. HA receptors mediate the recognition, internalization, and signaling of HA, influencing processes such as cell adhesion, migration, proliferation, and innate immune responses.

The best characterized HA receptors include CD44, a transmembrane glycoprotein expressed on many cell types; RHAMM (receptor for hyaluronan-mediated motility), which can be present on the cell surface or intracellular and links HA signaling to cytoskeletal dynamics; LYVE-1, a hyaluronan receptor on lymphatic endothelial cells that participates in HA transport and lymphatic function. A proteoglycan/stabilin family member, HARE or Stabilin-2, functions as an endocytic receptor for HA and mediates clearance of HA from the circulation.

HA-receptor signaling is often context dependent. Binding of HA to CD44 or RHAMM can activate mitogen-activated protein kinase pathways (e.g., ERK1/2), Rho family GTPases, and other cascades that regulate migration and proliferation. The effects of HA are also size-dependent: high molecular weight HA generally associates with anti-inflammatory or anti-angiogenic effects, whereas fragmented HA can promote inflammation and immune activation, sometimes via TLR2/TLR4 or CD44 itself.

Physiological and pathophysiological roles include tissue maintenance and wound repair, lymphatic trafficking, cancer cell invasion and metastasis, and fibrotic disease. Therapeutic strategies targeting HA receptors seek to modulate HA signaling in cancer, inflammation, and fibrosis, among other conditions.