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Tenascin-C drives persistence of organ fibrosis

Author

Listed:
  • Swati Bhattacharyya

    (Northwestern University Feinberg School of Medicine)

  • Wenxia Wang

    (Northwestern University Feinberg School of Medicine)

  • Luisa Morales-Nebreda

    (Northwestern University Feinberg School of Medicine)

  • Gang Feng

    (Northwestern University Feinberg School of Medicine)

  • Minghua Wu

    (University of Texas Medical School at Houston)

  • Xiaodong Zhou

    (University of Texas Medical School at Houston)

  • Robert Lafyatis

    (Boston University School of Medicine)

  • Jungwha Lee

    (Northwestern University Feinberg School of Medicine)

  • Monique Hinchcliff

    (Northwestern University Feinberg School of Medicine)

  • Carol Feghali-Bostwick

    (Medical University of South Carolina)

  • Katja Lakota

    (Northwestern University Feinberg School of Medicine)

  • G. R. Scott Budinger

    (Northwestern University Feinberg School of Medicine)

  • Kirtee Raparia

    (Northwestern University Feinberg School of Medicine)

  • Zenshiro Tamaki

    (Northwestern University Feinberg School of Medicine)

  • John Varga

    (Northwestern University Feinberg School of Medicine)

Abstract

The factors responsible for maintaining persistent organ fibrosis in systemic sclerosis (SSc) are not known but emerging evidence implicates toll-like receptors (TLRs) in the pathogenesis of SSc. Here we show the expression, mechanism of action and pathogenic role of endogenous TLR activators in skin from patients with SSc, skin fibroblasts, and in mouse models of organ fibrosis. Levels of tenascin-C are elevated in SSc skin biopsy samples, and serum and SSc fibroblasts, and in fibrotic skin tissues from mice. Exogenous tenascin-C stimulates collagen gene expression and myofibroblast transformation via TLR4 signalling. Mice lacking tenascin-C show attenuation of skin and lung fibrosis, and accelerated fibrosis resolution. These results identify tenascin-C as an endogenous danger signal that is upregulated in SSc and drives TLR4-dependent fibroblast activation, and by its persistence impedes fibrosis resolution. Disrupting this fibrosis amplification loop might be a viable strategy for the treatment of SSc.

Suggested Citation

  • Swati Bhattacharyya & Wenxia Wang & Luisa Morales-Nebreda & Gang Feng & Minghua Wu & Xiaodong Zhou & Robert Lafyatis & Jungwha Lee & Monique Hinchcliff & Carol Feghali-Bostwick & Katja Lakota & G. R. , 2016. "Tenascin-C drives persistence of organ fibrosis," Nature Communications, Nature, vol. 7(1), pages 1-14, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11703
    DOI: 10.1038/ncomms11703
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    Cited by:

    1. Xiaojie Cai & Maoying Han & Fangzhou Lou & Yang Sun & Qianqian Yin & Libo Sun & Zhikai Wang & Xiangxiao Li & Hong Zhou & Zhenyao Xu & Hong Wang & Siyu Deng & Xichen Zheng & Taiyu Zhang & Qun Li & Bin , 2023. "Tenascin C+ papillary fibroblasts facilitate neuro-immune interaction in a mouse model of psoriasis," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Wenxia Wang & Swarna Bale & Jun Wei & Bharath Yalavarthi & Dibyendu Bhattacharyya & Jing Jing Yan & Hiam Abdala-Valencia & Dan Xu & Hanshi Sun & Roberta G. Marangoni & Erica Herzog & Sergejs Berdnikov, 2022. "Fibroblast A20 governs fibrosis susceptibility and its repression by DREAM promotes fibrosis in multiple organs," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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