title: siRNA-targeting transforming growth factor-β type I receptor reduces wound scarring and extracellular matrix deposition of scar tissue.
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.
authors.affiliation: 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.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Wang
authors.affiliation: Department of Biology and Anatomy, National Defense Medical Center, Taipei City, Taiwan, Republic of China.
authors.forename: Nien-Hsien
authors.initials: NH
authors.lastname: Liou
authors.affiliation: School of Dentistry, National Defense Medical Center, Taipei City, Taiwan, Republic of China.
authors.forename: Juin-Hong
authors.initials: JH
authors.lastname: Cherng
authors.affiliation: Department of Dentistry, National Yang-Ming University, Taipei City, Taiwan, Republic of China.
authors.forename: Shu-Jen
authors.initials: SJ
authors.lastname: Chang
authors.affiliation: Department of Biology and Anatomy, National Defense Medical Center, Taipei City, Taiwan, Republic of China.
authors.forename: Kuo-Hsing
authors.initials: KH
authors.lastname: Ma
authors.affiliation: School of Dentistry, National Defense Medical Center, Taipei City, Taiwan, Republic of China.
authors.forename: Earl
authors.initials: E
authors.lastname: Fu
authors.affiliation: Department of Biology and Anatomy, National Defense Medical Center, Taipei City, Taiwan, Republic of China.
authors.forename: Jiang-Chuan
authors.initials: JC
authors.lastname: Liu
authors.affiliation: Department of Plastic and Reconstructive Surgery, Tri-Service General Hospital, Taipei City, Taiwan, Republic of China. Electronic address: niantzyy_dai@hotmail.com.
authors.forename: Niann-Tzyy
authors.initials: NT
authors.lastname: Dai
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D017439:Cicatrix, Hypertrophic / Q000473:pathology / Q000517:prevention & control / Q000628:therapy; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism* / Q000473:pathology; D005347:Fibroblasts / Q000473:pathology / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D006097:Granulation Tissue / Q000378:metabolism; D006801:Humans; D061251:Primary Cell Culture; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology*; D011817:Rabbits; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics / Q000502:physiology
chemical_list: C526317:CCN2 protein, human; D024042:Collagen Type I; D024061:Collagen Type III; D005353:Fibronectins; D034741:RNA, Small Interfering; D018125:Receptors, Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I