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Journal of Molecular Histology

, Volume 50, Issue 6, pp 503–514 | Cite as

Smad interacting protein 1 influences transforming growth factor-β1/Smad signaling in extracellular matrix protein production and hypertrophic scar formation

  • Xiaobing Fang
  • Xiaolong Hu
  • Zhao Zheng
  • Ke Tao
  • Hongtao Wang
  • Hao Guan
  • Jihong Shi
  • Peng Ji
  • Weixia Cai
  • Xiaozhi Bai
  • Xiongxiang Zhu
  • Juntao Han
  • Jiaqi LiuEmail author
  • Dahai HuEmail author
Original Paper
  • 165 Downloads

Abstract

The transforming growth factor (TGF)-β/Smad signal transduction pathway is closely associated with hypertrophic scar (HS) formation. Smad interacting protein 1 (SIP1) is a cytoplasmic protein that efficiently regulates Smad2-/3-dependent signaling within the TGF-β1 pathway. SIP1 influences collagen synthesis in the HS through a heretofore unknown mechanism. This study investigated the role of the SIP1-mediated TGF-β1/Smad signaling pathway in extracellular matrix (ECM) protein production and hypertrophic scarring. SIP1 expression was markedly lower in HS vs. normal skin (NS) tissue, and α-smooth muscle actin (α-SMA) content and collagen I/III (Col I/III) synthesis were inversely correlated with SIP1 expression. Furthermore, SIP1 inhibited Smad2/3 phosphorylation in vitro, and improved the collagen-based architecture of the scar while reducing collagen expression and overall scar formation in a rabbit ear model of HS. Based on these findings, we propose that SIP1 acts as a molecular modulator capable of altering Smad2-/3-facilitated signaling through the control of Smad phosphorylation, thus inhibiting α-SMA and collagen upregulation in fibroblasts and, ultimately, HS formation. The low SIP1 content in scar tissue also suggests that SIP1 (and positive regulation thereof) is a prospective target for selective HS drug therapy.

Keywords

Fibrosis Hypertrophic scar Smad Smad interacting protein 1 Transforming growth factor-β1 

Notes

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant Nos. 81171811, 81201470).

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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Xiaobing Fang
    • 1
  • Xiaolong Hu
    • 1
  • Zhao Zheng
    • 1
  • Ke Tao
    • 1
  • Hongtao Wang
    • 1
  • Hao Guan
    • 1
  • Jihong Shi
    • 1
  • Peng Ji
    • 1
  • Weixia Cai
    • 1
  • Xiaozhi Bai
    • 1
  • Xiongxiang Zhu
    • 1
  • Juntao Han
    • 1
  • Jiaqi Liu
    • 1
    Email author
  • Dahai Hu
    • 1
    Email author
  1. 1.Department of Burns and Cutaneous Surgery, Xijing HospitalFourth Military Medical UniversityXi’anChina

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