title: Heat Shock Protein 90 Inhibitor (17-AAG) Induces Apoptosis and Decreases Cell Migration/Motility of Keloid Fibroblasts.
abstract: BACKGROUND
  The regulation of apoptosis, proliferation, and migration of fibroblasts is altered in keloids. The 90-kDa heat shock protein (heat shock protein 90) is known to play a key role in such regulation. Therefore, the authors investigated whether the inhibition of heat shock protein 90 in keloid fibroblasts could induce apoptosis and attenuate keloid fibroblast proliferation and migration.
  
  
  METHODS
  The authors evaluated heat shock protein 90 expression in keloid tissues with immunohistochemistry. The authors used cell viability [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assays and annexin V/propidium iodide staining for apoptosis, a wound healing model and cell tracking system to assess cell migration, and Akt Western blotting analysis in keloid fibroblasts after inhibition of heat shock protein 90 with 17-allylaminodemethoxygeldanamycin (17-AAG).
  
  
  RESULTS
  The expression of heat shock protein 90 in keloid tissues was significantly increased compared with normal tissues. The 17-AAG-treated keloid fibroblasts showed significantly decreased proliferation, promotion of apoptosis, and decreased expression of Akt. Furthermore, a dose-dependent decrease in cell migration was noted after 17-AAG treatment of keloid fibroblasts. The 17-AAG-treated keloid fibroblasts had less directionality to the wound center and migrated a shorter distance.
  
  
  CONCLUSIONS
  The authors confirmed that the inhibition of heat shock protein 90 in keloid fibroblasts could promote apoptosis and attenuate proliferation and migration of keloid fibroblasts. Therefore, the authors think that the inhibition of heat shock protein 90 is a key factor in the regulation of biological processes in keloids. With further preclinical study, the authors will be able to apply these results clinically for keloid treatment.
authors.affiliation: Seoul, Republic of Korea From the Institute for Human Tissue Restoration, Department of Plastic and Reconstructive Surgery, and the Department of Medical Engineering, Yonsei University College of Medicine.
authors.forename: In Sik
authors.initials: IS
authors.lastname: Yun
authors.forename: Mi Hee
authors.initials: MH
authors.lastname: Lee
authors.forename: Dong Kyun
authors.initials: DK
authors.lastname: Rah
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Lew
authors.forename: Jong-Chul
authors.initials: JC
authors.lastname: Park
authors.forename: Won Jai
authors.initials: WJ
authors.lastname: Lee
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D016227:Benzoquinones / Q000494:pharmacology*; D015153:Blotting, Western; D016022:Case-Control Studies; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007627:Keloid / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D047029:Lactams, Macrocyclic / Q000494:pharmacology*
chemical_list: D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; C112765:tanespimycin