Gq protein mediates UVB-induced cyclooxygenase-2 expression by stimulating HB-EGF secretion from HaCaT human keratinocytes.

Ultraviolet (UV) radiation induces cyclooxygenase-2 expression to produce cellular responses including aging and carcinogenesis in skin. We hypothesised that heterotrimeric G proteins mediate UV-induced COX-2 expression by stimulating secretion of soluble HB-EGF (sHB-EGF). In this study, we aimed to elucidate the role and underlying mechanism of the alpha subunit of Gq protein (Galphaq) in UVB-induced HB-EGF secretion and COX-2 induction. We found that expression of constitutively active Galphaq (GalphaqQL) augmented UVB-induced HB-EGF secretion, which was abolished by knockdown of Galphaq with shRNA in HaCaT human keratinocytes. Galphaq was found to mediate the UVB-induced HB-EGF secretion by sequential activation of phospholipase C (PLC), protein kinase Cdelta (PKCdelta), and matrix metaloprotease-2 (MMP-2). Moreover, GalphaqQL mediated UVB-induced COX-2 expression in an HB-EGF-, EGFR-, and p38-dependent manner. From these results, we concluded that Galphaq mediates UV-induced COX-2 expression through activation of EGFR by HB-EGF, of which ectodomain shedding was stimulated through sequential activation of PLC, PKCdelta and MMP-2 in HaCaT cells.