論文

査読有り
2017年6月

Optimization of a murine and human tissue model to recapitulate dermal and pulmonary features of systemic sclerosis

PLOS ONE
  • Tomoya Watanabe
  • ,
  • Tetsuya Nishimoto
  • ,
  • Logan Mlakar
  • ,
  • Jonathan Heywood
  • ,
  • Maya Malaab
  • ,
  • Stanley Hoffman
  • ,
  • Carol Feghali-Bostwick

12
6
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1371/journal.pone.0179917
出版者・発行元
PUBLIC LIBRARY SCIENCE

The murine bleomycin (BLM)-induced fibrosis model is the most widely used in systemic sclerosis (SSc) studies. It has been reported that systemic delivery of BLM via continuous diffusion from subcutaneously implanted osmotic minipumps can cause fibrosis of the skin, lungs, and other internal organs. However, the mouse strain, dosage of BLM, administration period, and additional important features differ from one report to the next. In this study, by employing the pump model in C57BL/6J mice, we show a dose-dependent increase in lung fibrosis by day 28 and a transient increase in dermal thickness. Dermal thickness and the level of collagen in skin treated with high-dose BLM was significantly higher than in skin treated with low dose BLM or vehicle. A reduction in the thickness of the adipose layer was noted in both high and low dose groups at earlier time points suggesting that the loss of the fat layer precedes the onset of fibrosis. High-dose BLM also induced dermal fibrosis and increased expression of fibrosis-associated genes ex vivo in human skin, thus confirming and extending the in vivo findings, and demonstrating that a human organ culture model can be used to assess the effect of BLM on skin. In summary, our findings suggest that the BLM pump model is an attractive model to analyze the underlying mechanisms of fibrosis and test the efficacy of potential therapies. However, the choice of mouse strain, duration of BLM administration and dose must be carefully considered when using this model.

Web of Science ® 被引用回数 : 7

リンク情報
DOI
https://doi.org/10.1371/journal.pone.0179917
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000404537300029&DestApp=WOS_CPL

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