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

• Published in: Biochemical and biophysical research communications 2010-03, Vol.393 (2), p.190-195
• Main Authors: Seo, MiRan, Juhnn, Yong-Sung
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; AGING; CARCINOGENESIS; CELL PROLIFERATION; Cell Transformation, Neoplastic - metabolism; COX-2; Cyclooxygenase 2 - biosynthesis; DENSITY MATRIX; Enzyme Activation; GTP-ASES; GTP-Binding Protein alpha Subunits, Gq-G11 - metabolism; Gαq; HB-EGF; Heparin-binding EGF-like Growth Factor; Humans; Intercellular Signaling Peptides and Proteins - metabolism; Keratinocytes; Keratinocytes - enzymology; Keratinocytes - radiation effects; Matrix Metalloproteinase 2 - metabolism; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphoinositide Phospholipase C - metabolism; Protein Kinase C - metabolism; Protein Kinase C beta; Receptor, Epidermal Growth Factor - agonists; Receptor, Epidermal Growth Factor - metabolism; SECRETION; SKIN; Skin Aging; Skin Neoplasms - enzymology; Ultraviolet Rays; UVB
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2010.01.085

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 α subunit of Gq protein (Gαq) in UVB-induced HB-EGF secretion and COX-2 induction. We found that expression of constitutively active Gαq (GαqQL) augmented UVB-induced HB-EGF secretion, which was abolished by knockdown of Gαq with shRNA in HaCaT human keratinocytes. Gαq was found to mediate the UVB-induced HB-EGF secretion by sequential activation of phospholipase C (PLC), protein kinase Cδ (PKCδ), and matrix metaloprotease-2 (MMP-2). Moreover, GαqQL mediated UVB-induced COX-2 expression in an HB-EGF-, EGFR-, and p38-dependent manner. From these results, we concluded that Gαq mediates UV-induced COX-2 expression through activation of EGFR by HB-EGF, of which ectodomain shedding was stimulated through sequential activation of PLC, PKCδ and MMP-2 in HaCaT cells.