論文

査読有り 国際誌
2019年1月22日

A Human Skin Model Recapitulates Systemic Sclerosis Dermal Fibrosis and Identifies COL22A1 as a TGFβ Early Response Gene that Mediates Fibroblast to Myofibroblast Transition.

Genes
  • Tomoya Watanabe
  • ,
  • DeAnna Baker Frost
  • ,
  • Logan Mlakar
  • ,
  • Jonathan Heywood
  • ,
  • Willian A da Silveira
  • ,
  • Gary Hardiman
  • ,
  • Carol Feghali-Bostwick

10
2
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.3390/genes10020075

: Systemic sclerosis (SSc) is a complex multi-system autoimmune disease characterized by immune dysregulation, vasculopathy, and organ fibrosis. Skin fibrosis causes high morbidity and impaired quality of life in affected individuals. Animal models do not fully recapitulate the human disease. Thus, there is a critical need to identify ex vivo models for the dermal fibrosis characteristic of SSc. We identified genes regulated by the pro-fibrotic factor TGFβ in human skin maintained in organ culture. The molecular signature of human skin overlapped with that which was identified in SSc patient biopsies, suggesting that this model recapitulates the dermal fibrosis characteristic of the human disease. We further characterized the regulation and functional impact of a previously unreported gene in the setting of dermal fibrosis, COL22A1, and show that silencing COL22A1 significantly reduced TGFβ-induced ACTA2 expression. COL22A1 expression was significantly increased in dermal fibroblasts from patients with SSc. In summary, we identified the molecular fingerprint of TGFβ in human skin and demonstrated that COL22A1 is associated with the pathogenesis of fibrosis in SSc as an early response gene that may have important implications for fibroblast activation. Further, this model will provide a critical tool with direct relevance to human disease to facilitate the assessment of potential therapies for fibrosis.

リンク情報
DOI
https://doi.org/10.3390/genes10020075
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30678304
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409682

エクスポート
BibTeX RIS