Details

Autor(en) / Beteiligte

• Oh, Jang-Hee
• Kim, Aeyung
• Park, Jong-Min
• Kim, Shin-Hyoung
• Chung, An-Sik

Titel

Ultraviolet B-induced matrix metalloproteinase-1 and -3 secretions are mediated via PTEN/Akt pathway in human dermal fibroblasts

Ist Teil von

• Journal of cellular physiology, 2006-12, Vol.209 (3), p.775-785

Ort / Verlag

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

Erscheinungsjahr

2006

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• Matrix Metalloproteinases (MMPs) are crucial enzymes for ultraviolet irradiation‐induced photoaging in human skin. Ultraviolet B (UVB) stimulates dermal fibroblasts to increase MMP‐1 and ‐3 expression and extracellular matrix (ECM) degradation in photoaging. We investigated whether phosphatase and tensin homolog (PTEN)/Akt pathway is involved in secretions of MMP‐1 and ‐3 in human dermal fibroblasts. 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 casein kinase 2 inhibitor, 5,6‐dichloro‐1‐β‐D‐ribofuranosyl‐benzimidazole, inhibited their phosphorylations and MMP‐1 and ‐3 secretions. Transfection of wild‐type 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 irradiation increases PTEN and Akt phosphorylation in human dermal fibroblasts, and these inhibition of PTEN and activation of Akt by phosphorylation are involved in UVB‐induced MMP‐1 and ‐3 secretions partly through upregulation of AP‐1 activity. J. Cell. Physiol. 209: 775–785, 2006. © 2006 Wiley‐Liss, Inc.