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J Invest Dermatol. 2014 Jul;134(7):2016-2025. doi: 10.1038/jid.2014.84. Epub 2014 Feb 13.

siRNA-targeting transforming growth factor-β type I receptor reduces wound scarring and extracellular matrix deposition of scar tissue.

Author information

1
Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei City, Taiwan, Republic of China; Burn Center, Tri-Service General Hospital, Taipei City, Taiwan, Republic of China.
2
Department of Biology and Anatomy, National Defense Medical Center, Taipei City, Taiwan, Republic of China.
3
School of Dentistry, National Defense Medical Center, Taipei City, Taiwan, Republic of China.
4
Department of Dentistry, National Yang-Ming University, Taipei City, Taiwan, Republic of China.
5
Department of Plastic and Reconstructive Surgery, Tri-Service General Hospital, Taipei City, Taiwan, Republic of China. Electronic address: niantzyy_dai@hotmail.com.

Erratum in

  • J Invest Dermatol. 2014 Nov;134(11):2852.

Abstract

Hypertrophic scarring is related to persistent activation of transforming growth factor-β (TGF-β)/Smad signaling. In the TGF-β/Smad signaling cascade, the TGF-β type I receptor (TGFBRI) phosphorylates Smad proteins to induce fibroblast proliferation and extracellular matrix deposition. In this study, we inhibited TGFBRI gene expression via TGFBRI small interfering RNA (siRNA) to reduce fibroblast proliferation and extracellular matrix deposition. Our results demonstrate that downregulating TGFBRI expression in cultured human hypertrophic scar fibroblasts significantly suppressed cell proliferation and reduced type I collagen, type III collagen, fibronectin, and connective tissue growth factor (CTGF) mRNA, and type I collagen and fibronectin protein expression. In addition, we applied TGFBRI siRNA to wound granulation tissue in a rabbit model of hypertrophic scarring. Downregulating TGFBRI expression reduced wound scarring, the extracellular matrix deposition of scar tissue, and decreased CTGF and α-smooth muscle actin mRNA expression in vivo. These results suggest that TGFBRI siRNA could be applied clinically to prevent hypertrophic scarring.

PMID:
24670383
DOI:
10.1038/jid.2014.84
[Indexed for MEDLINE]
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