title: Peroxisome proliferator-activated receptor δ modulates MMP-2 secretion and elastin expression in human dermal fibroblasts exposed to ultraviolet B radiation.
abstract: BACKGROUND
  Changes in skin connective tissues mediated by ultraviolet (UV) radiation have been suggested to cause the skin wrinkling normally associated with premature aging of the skin. Recent investigations have shown that peroxisome proliferator-activated receptor (PPAR) δ plays multiple biological roles in skin homeostasis.
  
  
  OBJECTIVE
  We attempted to investigate whether PPARδ modulates elastin protein levels and secretion of matrix metalloproteinase (MMP)-2 in UVB-irradiated human dermal fibroblasts (HDFs) and mouse skin.
  
  
  METHODS
  These studies were undertaken in primary HDFs or HR-1 hairless mice using Western blot analyses, small interfering (si)RNA-mediated gene silencing, and Fluorescence microscopy.
  
  
  RESULTS
  In HDFs, UVB irradiation induced increased secretion of MMP-2 and reduced levels of elastin. Activation of PPARδ by GW501516, a ligand specific for PPARδ, markedly attenuated UVB-induced MMP-2 secretion with a concomitant increase in the level of elastin. These effects were reduced by the presence of siRNAs against PPARδ or treatment with GSK0660, a specific inhibitor of PPARδ. Furthermore, GW501516 elicited a dose- and time-dependent increase in the expression of elastin. Modulation of MMP-2 secretion and elastin levels by GW501516 was associated with a reduction in reactive oxygen species (ROS) production in HDFs exposed to UVB. Finally, in HR-1 hairless mice, administration of GW501516 significantly reduced UVB-induced MMP-2 expression with a concomitant increase in elastin levels, and these effects were significantly reduced by the presence of GSK0660.
  
  
  CONCLUSIONS
  Our results suggest that PPARδ-mediated modulation of MMP-2 secretion and elastin expression may contribute to the maintenance of skin integrity by inhibiting ROS generation.
authors.affiliation: Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea.
authors.forename: Sun Ah
authors.initials: SA
authors.lastname: Ham
authors.affiliation: Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea.
authors.forename: Taesik
authors.initials: T
authors.lastname: Yoo
authors.affiliation: Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea.
authors.forename: Jung Seok
authors.initials: JS
authors.lastname: Hwang
authors.affiliation: Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea.
authors.forename: Eun Sil
authors.initials: ES
authors.lastname: Kang
authors.affiliation: Department of Nursing, Semyung University, Jechon, Chungbuk, Republic of Korea.
authors.forename: Kyung Shin
authors.initials: KS
authors.lastname: Paek
authors.affiliation: Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea.
authors.forename: Chankyu
authors.initials: C
authors.lastname: Park
authors.affiliation: Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea.
authors.forename: Jin-Hoi
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea.
authors.forename: Jeong Tae
authors.initials: JT
authors.lastname: Do
authors.affiliation: Department of Animal Biotechnology, Konkuk University, Seoul, Republic of Korea. Electronic address: hgseo@konkuk.ac.kr.
authors.forename: Han Geuk
authors.initials: HG
authors.lastname: Seo
mesh_terms: D000818:Animals; D004307:Dose-Response Relationship, Radiation; D004549:Elastin / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006706:Homeostasis; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D047494:PPAR delta / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012867:Skin / Q000378:metabolism*; D013450:Sulfones / Q000737:chemistry; D013876:Thiophenes / Q000737:chemistry; D014466:Ultraviolet Rays; D014945:Wound Healing
chemical_list: C529769:GSK0660; D047494:PPAR delta; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D013450:Sulfones; D013876:Thiophenes; D004549:Elastin; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse
keywords: Elastin; HDFs; MMP-2; PPARδ; UVB