title: Versican gene: regulation by the β-catenin signaling pathway plays a significant role in dermal papilla cell aggregative growth.
abstract: BACKGROUND
  Dermal papilla cells (DPCs), which exhibit a multilayer aggregative growth character in in vitro culture, are closely related to induction of hair follicles (HFs) formation, and are associated with the development and cycle regulation of HFs. Versican, a large chondroitin sulfate proteoglycan and one of the major components of the extracellular matrix, plays an essential role in hair follicle formation. And also the Wnt/β-catenin signaling pathway performs a crutial function in induction during hair follicle growth and embryogenesis.
  
  
  OBJECTIVE
  To characterize the role of versican and β-catenin in regulating DPCs aggregative growth, and to explore the versican gene expression regulation mechanism by TCF-4/β-catenin signaling pathway.
  
  
  METHODS
  We first cultured DPCs at different passages, and detected the change in β-catenin and versican expression in DPCs of various passages by RT-PCR and Western blot. Then we knockdowned the versican and β-catenin gene, evaluated and verificated the binding capability of TCF-4/β-catenin to TOP elements in versican gene promoter region at varied passage DPCs by EMSA and ChIP Assay, finally observed the effect of Wnt/β-catenin pathway inhibition on DPC aggregative growth.
  
  
  RESULTS
  With the increase of passage, DPCs lost the aggregative property, the versican mRNA and protein level in DPCs was on a gradual decline, while not significant declining tendency of β-catenin. The mRNA of both β-catenin and versican reduced simultaneously after β-catenin siRNA transfection. The binding ability of TCF-4/β-catenin of varied-passage DPCs to cultured versican promoters diminished with the increase of DPC passages. And versican inhibition or Wnt/β-catenin pathway blocking could both produce considerable effect on the aggregative growth of low-passage DPCs.
  
  
  CONCLUSIONS
  Wnt/β-catenin signal transducting system regulates DPC aggregative growth through modifying versican expression by means of acting on the versican gene upstream promoter.
authors.affiliation: Department of Plastic Surgery, Daping Hospital, Research Institute of Surgery, Third Military Medical University, Chongqing 400042, PR China.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Yang
authors.forename: Yuanchao
authors.initials: Y
authors.lastname: Li
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Jinjin
authors.initials: J
authors.lastname: Wu
authors.forename: Guihong
authors.initials: G
authors.lastname: Yang
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.forename: Yang
authors.initials: Y
authors.lastname: Gao
authors.forename: Yuangang
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000328:Adult; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism; D002449:Cell Aggregation; D002478:Cells, Cultured; D020405:Dermis / Q000166:cytology* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D018859:Hair Follicle / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism*; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D000073940:Transcription Factor 4; D014157:Transcription Factors / Q000378:metabolism; D053675:Versicans / Q000037:antagonists & inhibitors / Q000235:genetics*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C495270:CTNNB1 protein, human; D034741:RNA, Small Interfering; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D014157:Transcription Factors; C508322:VCAN protein, human; D051176:beta Catenin; D053675:Versicans