title: Prolonged activation of ERK contributes to the photorejuvenation effect in photodynamic therapy in human dermal fibroblasts.
abstract: Photodynamic therapy (PDT) is known to be effective in the photorejuvenation of photoaged skin. However, the molecular mechanisms of rejuvenation by PDT remain elusive. In this study, we aimed to understand the molecular events occurring during the photorejuvenation after PDT in dermal fibroblasts in vitro. First, we found that PDT conditions resulted in an increased fibroblast proliferation and motility in vitro. Under this condition, cells had increased intracellular reactive oxygen species (ROS) production. Importantly, PDT induced a prolonged activation of extracellular signal-regulated kinase (ERK) with a corresponding increase in matrix metalloproteinase (MMP)-3 and collagen type Iα messenger RNA and protein. Moreover, inhibition of PDT-induced ERK activation significantly suppressed fibroblast proliferation and expression of MMP-3 and collagen type Iα following PDT. In addition, NAC (an antioxidant) inhibited PDT-induced fibroblast proliferation and ERK activation indicating that prolonged ERK activation and intracellular ROS contribute to the proliferation of fibroblasts and the dermal remodeling process for skin rejuvenation. We also identified increased collagen volume and decreased elastotic materials that are used as markers of photoaging in human skin samples using histochemical studies. Results from this study suggest that intracellular ROS stimulated by PDT in dermal fibroblasts lead to prolonged activation of ERK and, eventually, fibroblast proliferation and activation. Our data thus reveal a molecular mechanism underlying the skin rejuvenation effect of PDT.
authors: Department of Dermatology, Ajou University School of Medicine, Suwon, Republic of Korea.
authors: Yong Hyun
authors: YH
authors: Jang
authors: Gi-Bang
authors: GB
authors: Koo
authors: Joo-Young
authors: JY
authors: Kim
authors: You-Sun
authors: YS
authors: Kim
authors: You Chan
authors: YC
authors: Kim
mesh_terms: D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D020405:Dermis / Q000166:cytology*; D004789:Enzyme Activation / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D010778:Photochemotherapy / Q000379:methods*; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012060:Rejuvenation / Q000502:physiology*; D015595:Skin Aging / Q000473:pathology / Q000502:physiology*
chemical_list: D024042:Collagen Type I; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3