title: Potential Molecular Mechanisms Involved in 5-Aminolevulinic Acid-Based Photodynamic Therapy against Human Hypertrophic Scars.
abstract: BACKGROUND
  Hypertrophic scars are manifestations of an abnormal process of tissue repair. Although photodynamic therapy is a promising treatment, details of the mechanisms underlying its inhibitory effects remain to be elucidated.
  
  
  METHODS
  Fibroblasts were isolated from human hypertrophic scar specimens and subjected to photodynamic therapy; 5-aminolevulinic acid was used as a photosensitizer. The accumulation of 5-aminolevulinic acid-derived protoporphyrin IX was detected under fluorescence microscopy. The potential cytotoxicity of 5-aminolevulinic acid alone and with photodynamic therapy was measured by 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide. Hoechst 33258 staining and flow cytometry were conducted to search for clues to apoptosis. Protein and/or mRNA expression levels of apoptosis-related pathways and other hypertrophic scar pathogenesis-associated signaling were investigated by Western blot analysis and/or real-time polymerase chain reaction.
  
  
  RESULTS
  Protoporphyrin IX accumulation peak was achieved at 1.0 mM 5-aminolevulinic acid. 5-Aminolevulinic acid ranging from 0 to 1.0 mM was demonstrated to be noncytotoxic but reduced cell viabilities in a dose-dependent manner with acid-based photodynamic therapy were demonstrated. Reduction of cell viability was attributed mainly to cell apoptosis and probably to mechanisms such as up-regulation of p53/p21, Bax/Bcl-2 ratio, and cleaved caspase-3. Concurrently, deregulation of transforming growth factor-β1-mediated signaling, serving as another putative mechanism underlying hypertrophic scar formation, was found to be reversely modulated in response to acid-based photodynamic therapy.
  
  
  CONCLUSIONS
  The p53-related apoptosis pathway and transforming growth factor-β1-mediated signaling may be important factors used to predict and evaluate the treatment outcomes of 5-aminolevulinic acid-based photodynamic therapy used in hypertrophic scar patients.
  
  
  METHODS
  Therapeutic, V.
authors.affiliation: Shanghai, People's Republic of China From the Department of Plastic and Reconstructive Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University.
authors.forename: Mengling
authors.initials: M
authors.lastname: Chang
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Ma
authors.forename: Tianxiang
authors.initials: T
authors.lastname: Ouyang
authors.forename: Jun
authors.initials: J
authors.lastname: Lin
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiao
authors.forename: Huiping
authors.initials: H
authors.lastname: Chen
authors.forename: Jie
authors.initials: J
authors.lastname: Yu
authors.forename: Yingying
authors.initials: Y
authors.lastname: Huang
authors.forename: Miao
authors.initials: M
authors.lastname: Xu
mesh_terms: D000622:Aminolevulinic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D017439:Cicatrix, Hypertrophic / Q000188:drug therapy* / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology* / Q000627:therapeutic use; D011524:Protoporphyrins / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX