title: Suppression of UVB-induced HIF-1α up-regulation by hyperoxia does not prevent wrinkle formation associated with increased MMPs activity in mouse skin.
abstract: This study investigated whether the suppression of hypoxia-inducible factor (HIF)-1α up-regulation prevents high-dose and long-term UVB-induced wrinkle formation and angiogenesis associated with increased matrix metalloproteinase (MMP)-2 and MMP-9 activities. Twenty-four hairless mice were assigned to three groups: 1) control, 2) UVB-irradiation (UVB), and 3) UVB-irradiation followed by hyperoxia (UVB+HO). The backs of the mice were exposed to UVB irradiation three times a week for 10 weeks. To suppress UVB-induced cutaneous HIF-1α up-regulation, the mice were exposed to hyperoxia (90% oxygen) for 2 h immediately after each UVB irradiation. The UVB and UVB+HO groups had significantly increased degrees of wrinkle formation, dermal blood vessel density, and MMP-2 and MMP-9 activities compared with the control group. HIF-1α expression levels were significantly higher in the UVB group than in the control group whereas these levels remained unchanged in the UVB+HO groups. The activity of type 1 collagenase which digests collagen type 1 (a main component of the dermis), was similar in all groups; furthermore, the dermal soluble collagen content was similar in all groups. These results suggest that the suppression of increases in HIF-1α levels alone is insufficient to restrain wrinkle formation caused by higher doses and longer periods of the UVB irradiation that led to the up-regulation of MMP-2 and MMP-9 activities.
authors.affiliation: Laboratory of Tissue Plasticity Science, Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Kawada
authors.forename: Naokata
authors.initials: N
authors.lastname: Ishii
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D018496:Hyperoxia / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000201:enzymology / Q000528:radiation effects*; D015595:Skin Aging; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000528:radiation effects*
chemical_list: D017931:DNA Primers; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9