title: Inhibition of collagen synthesis by IWR-1 in normal and keloid-derived skin fibroblasts.
abstract: OBJECTIVE
  Keloid is a benign tumor that is characterized by the hyperproliferation of dermal fibroblasts and excessive deposition of extracellular matrix (ECM) especially the collagen. Aberrant activation of Wnt/β-catenin signaling is implicated in the pathogenesis of keloid. In this study, we investigated the effects of IWR-1, a small molecule inhibitor for Wnt/β-catenin signaling via the inhibition of tankyrase, on production of collagen and matrix metalloproteinase (MMP) in dermal fibroblasts.
  
  
  METHODS
  We cultured human normal skin- and keloid-derived fibroblasts, then treated with IWR-1. The effects of IWR-1 on collagen and MMP production were determined by Western blot, ELISA and zymography.
  
  
  RESULTS
  IWR-1 significantly suppressed the proliferation and migration of both the normal and keloid fibroblasts. IWR-1 also inhibited the production and secretion of type I collagen from the fibroblasts. In addition, IWR-1 significantly increased the expression of MMPs, such as MMP-1, MMP-3 and MMP-13, along with the increase of gelatinase activity. These results suggest that inhibitory effect of IWR-1 on collagen production may be related with the increased MMP activity.
  
  
  CONCLUSIONS
  This study provides the possible action mechanism of IWR-1 on regulation of collagen expression, on which to base further investigation for preventing skin fibrotic diseases such as keloid.
authors.affiliation: Department of Dermatology, The Third Hospital of Jilin University, Changchun, Jilin, China; Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Zhou
authors.affiliation: Department of Orthopaedics, The Third Hospital of Jilin University, Changchun, Jilin, China.
authors.forename: Wei-Tian
authors.initials: WT
authors.lastname: Yin
authors.affiliation: Department of Dermatology, The Third Hospital of Jilin University, Changchun, Jilin, China.
authors.forename: Ri-Hua
authors.initials: RH
authors.lastname: Jiang
authors.affiliation: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Jin-Hyup
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Chang-Deok
authors.initials: CD
authors.lastname: Kim
authors.affiliation: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Republic of Korea; Skin Med Company, Daejeon, Republic of Korea.
authors.forename: Jeung-Hoon
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Dermatology, The Third Hospital of Jilin University, Changchun, Jilin, China. Electronic address: Zhumingji33@163.com.
authors.forename: Ming Ji
authors.initials: MJ
authors.lastname: Zhu
authors.affiliation: Department of Dermatology and Institute of Health Sciences, School of Medicine, Gyeongsang National University & Hospital, Jinju, Republic of Korea. Electronic address: yoontj@gnu.ac.kr.
authors.forename: Tae-Jin
authors.initials: TJ
authors.lastname: Yoon
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D017364:Collagenases / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007094:Imides / Q000494:pharmacology*; D007627:Keloid / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011804:Quinolines / Q000494:pharmacology*; D012867:Skin / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: C585534:IWR-1 compound; D007094:Imides; D011804:Quinolines; D003094:Collagen; D017364:Collagenases
keywords: Collagen; Fibroblasts; IWR-1; Keloid; Matrix metalloproteinase