title: Effect of heat shock protein 47 on collagen synthesis of keloid in vivo.
abstract: Keloid is regarded as a fibroproliferative disorder with excessive accumulation of extracellular matrix. However, the molecular mechanism of keloid formation is not well understood and no treatment modality is consistently effective. Heat shock protein 47 (HSP47) is known as a collagen-specific molecular chaperone which plays a critical role in collagen biosynthesis. Results of our previous in vitro experiments demonstrated that HSP47 might be an important reason for excessive collagen accumulation in regard to keloid formation. Our objective is to investigate whether HSP47 has an influence on collagen metabolism in animal keloid models. The constructed plasmids, carrying HSP47-small hairpin RNA (shRNA), were transfected into animal keloid models, in comparison with the control groups. After transfection, the mRNA and protein expression of HSP47 and collage type I were detected by quantitative real-time PCR and Western blot. Both the mRNA and protein levels of HSP47 in animal keloid models were decreased dramatically after transfection of the HSP47- shRNA plasmid, in comparison with the control group. Following the down-regulation of HSP47, we found that the volume of animal keloid models and the major collagen expression were reduced correspondingly. Combining the results of our previous in vitro experiment results, we suggest that overexpression of HSP47 in keloid fibroblast cells could induce excessive collagen accumulation by enhancing collagen synthesis, which not only presents a possible mechanism of keloid formation, but also offers a therapeutic potential of RNA interference to HSP47 for the treatment of keloids and other fibroproliferative disorders.
authors.affiliation: Department of Burns and Plastic Surgery, West China Hospital, Sichuan University, Sichuan, China.
authors.forename: Jun-Jie
authors.initials: JJ
authors.lastname: Chen
authors.forename: Pei-Sheng
authors.initials: PS
authors.lastname: Jin
authors.forename: Sha
authors.initials: S
authors.lastname: Zhao
authors.forename: Ying
authors.initials: Y
authors.lastname: Cen
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Xue-Wen
authors.initials: XW
authors.lastname: Xu
authors.forename: Wei-Qiang
authors.initials: WQ
authors.lastname: Duan
authors.forename: Huai-Sheng
authors.initials: HS
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D015153:Blotting, Western; D003094:Collagen / Q000096:biosynthesis* / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D050958:HSP47 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D007627:Keloid / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D050958:HSP47 Heat-Shock Proteins; D012333:RNA, Messenger; D003094:Collagen