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TGF-β-mediated upregulation of brachyury contributes to constitutively up-regulated type I collagen expression in skin fibroblasts: possible role in systemic sclerosis

  • Investigative Report
  • Published:
European Journal of Dermatology Aims and scope

Abstract

Background

Previous reports have shown that epithelial-to-mesenchymal transition (EMT) indicates the importance of transforming growth factor-13 (TGF-β) signalling in the pathogenesis of systemic sclerosis (SSc). However, the underlying molecular mechanisms of EMT are not fully understood.

Objectives

Brachyury, an evolutionarily conserved transcription factor, was recently identified as an important factor that promotes EMT in human carcinoma cell lines. However, there is no evidence indicating that brachyury is involved in EMT in SSc.

Materials and Methods

The expression of brachyury and collagen was investigated in cultures of dermal fibroblasts and skin sections derived from SSc patients and healthy controls. Brachyury and collagen expression were determined by immunohistochemistry and immunoblotting, respectively, and inRNA for both was analysed using real-time PCR.

Results

Brachyury was overexpressed in SSc dermal fibroblasts both in vivo and in vitro, and this overexpression was inhibited by TGF-β1 inhibitor. Brachyury siRNA reduced mRNA and protein expression levels of type I collagen in normal and SSc dermal fibroblasts, but did not decrease the levels of major disease-related cytokines. Furthermore, brachyury levels were significantly increased in skin samples of SSc patients relative to healthy controls.

Conclusions

The up-regulation of brachyury in response to activated endogenous TGF-β signalling may play a role in constitutive up-regulation of collagen in SSc fibroblasts. Further studies assessing the regulatory mechanism of tissue fibrosis induced by brachyury in SSc skin may lead to a better understanding of the pathogenesis, new diagnostic methods, and new therapeutic approaches using siRNAs.

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Acknowledgement

This study was supported in by a grant for NSFC. The funders had no rote in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Author notes

  1. These authors contributed equally

Authors and Affiliations

  1. Department of Dermatology, Changzheng Hospital, Second Military Medicai University, No. 415 Fengyang Road, Shanghai, 200003, China

    Liang Teng, Guotai Yao, Rui Gao, Yilin Wang, Wenting Lin, Yi Jin, Yan Wang, Hong Chen, Zhongzhi Wang & Jianghan Chen

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  1. Liang Teng
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  2. Guotai Yao
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  7. Yan Wang
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Correspondence to Zhongzhi Wang or Jianghan Chen.

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Acknowledgement and disclosures. Conflicts of interest: The authors have no conflicts of interest to declare.

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Teng, L., Yao, G., Gao, R. et al. TGF-β-mediated upregulation of brachyury contributes to constitutively up-regulated type I collagen expression in skin fibroblasts: possible role in systemic sclerosis. Eur J Dermatol 29, 359–365 (2019). https://doi.org/10.1684/ejd.2019.3607

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  • DOI: https://doi.org/10.1684/ejd.2019.3607

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