Role of PTEN in UVB-induced MMP secretion in cultured human dermal fibroblasts

Abstract

Matrix Metalloproteinases (MMPs) are crucial enzymes for ultraviolet irradiation-induced photoageing in human skin, and are considered to have a critical role in dermal component degradation including collagen degradation. Ultraviolet B (UVB) stimulates dermal fibroblasts to increase MMP-1 and -3 expression and extracellular matrix degradation in photoageing. While epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK) pathway has been accepted as a major regulation pathway for MMP-1 and -3 induction upon UVB irradiation, it was newly investigated whether phosphatase and tensin homolog (PTEN)/Akt pathway is involved in secretions of MMP-1 and -3 in human dermal fibroblasts, as a downstream target of casein kinase 2 (CK2). The increase in MMP-1 and -3 expression and secretion occurred along with the increase in PTEN and Akt phosphorylation by UVB irradiation in a dose and time-dependent manner. However, treatment with a CK2 inhibitor, 5,6-dichloro-1-β-D-ribofuranosyl-benzimidazole, inhibited their phosphorylations and MMP-1 and -3 secretions. Transfection of wildtype PTEN (Wt-PTEN) decreased basal and UVB-induced MMP-1 and -3 secretions, as well as activator protein-1 (AP-1) activity, while transfection of small interference RNA of PTEN (siRNA-PTEN), phosphatase-inactive PTEN (C124S-PTEN), or lipid phosphatase-inactive PTEN (G129E-PTEN) increased basal or UVB-induced MMP-1 and -3 secretions and AP-1 activity. Transfection of constitutively-active Akt (Myr-Akt) also increased basal or UVB-induced MMP-1 and -3 secretions, as well as AP-1 activity. However, transfection of kinase-inactive Akt (K179M-Akt) decreased their secretions, but showed no significant change of AP-1 activity without UVB irradiation, and a significant increase of AP-1 activity with UVB irradiation. Treatment with the phosphatidylinositol 3-kinase inhibitors, LY294002 or wortmannin, downregulated basal and UVB-induced MMP-1 and -3 secretions. In conclusion, UVB irradiat...