Regulation of hyaluronan production by β2 adrenergic receptor signaling

Hyaluronan (HA), the main component of the extracellular matrix, is involved in tissue elasticity and cell scaffolding, and in progression of conditions such as cancer, inflammation and wound healing. Signaling by G protein coupled receptor (GPCR) activation increases expression of hyaluronan synthase (HAS) and HA production. The β2 adrenergic receptor (β2AR) is a catecholamine-liganded GPCR that is involved in cancer progression and wound healing. Since HA and β2AR are involved in a common pathology, we investigated whether β2AR signaling regulates HA production.

After stimulating β2AR-expressing cells with a β agonist, the amount of HA in the culture medium was measured and HAS expression was examined by real-time PCR. A variety of signaling molecule inhibitors were used to identify signaling pathways that alter HAS expression.

β2AR activation increased HA production and enhanced HAS2 expression. The increase in HAS2 expression by β2AR activation occurred via the Gs - adenylyl cyclase - PKA - CREB signal transduction pathway.

Downstream signal transduction by β2AR activation increased HA production by enhancing transcription of the HAS2 gene. This study suggests that β2AR is a GPCR that regulates HA production, and that stimulation with a catecholamine (β2 agonist) can regulate HA production.

β2AR may function through regulation of HA production in cancer progression and wound healing.