title: Shikonin reduces TGF-β1-induced collagen production and contraction in hypertrophic scar-derived human skin fibroblasts.
abstract: Hypertrophic scarring/hypertrophic scars (HS) is a highly prevalent condition following burns and trauma wounds. Numerous studies have demonstrated that transforming growth factor-β1 (TGF‑β1) plays an essential role in the wound healing process by regulating cell differentiation, collagen production and extracellular matrix degradation. The increased expression of TGF-β1 is believed to result in the formation of HS. Shikonin (SHI), an active component extracted from the Chinese herb, Radix Arnebiae, has previously been found to downregulate the expression of TGF-β1 in keratinocyte/fibroblast co-culture conditioned medium. In view of this, in this study, we aimed to further investigate the effects of SHI on TGF-β1-stimulated hypertrophic scar-derived human skin fibroblasts (HSFs) and examined the underlying mechanisms. Cell viability and proliferation were measured using alamarBlue and CyQUANT assays. The total amount of collagen and cell contraction were examined using Sirius red staining and the cell contraction assay kit. Gene expression and signalling pathway activation were detected using reverse transcription-quantitative polymerase chain reaction and western blot analysis. Our results revealed that SHI reduced TGF-β1‑induced collagen production through the ERK/Smad signalling pathway and attenuated TGF-β1‑induced cell contraction by downregulating α-smooth muscle actin (αSMA) expression in the HSFs. The data from this study provide evidence supporting the potential use of SHI as a novel treatment for HS.
authors.affiliation: Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4059, Australia.
authors.forename: Chen
authors.initials: C
authors.lastname: Fan
authors.affiliation: Cancer Research Program, Translational Research Institute, Queensland University of Technology, Brisbane, Queensland 4102, Australia.
authors.forename: Ying
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4059, Australia.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Su
authors.affiliation: Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4059, Australia.
authors.forename: Xufang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4059, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Leavesley
authors.affiliation: Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4059, Australia.
authors.forename: Zee
authors.initials: Z
authors.lastname: Upton
mesh_terms: D000199:Actins / Q000096:biosynthesis; D017439:Cicatrix, Hypertrophic / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003094:Collagen / Q000096:biosynthesis*; D015536:Down-Regulation / Q000187:drug effects; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009285:Naphthoquinones / Q000494:pharmacology*; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D000199:Actins; D009285:Naphthoquinones; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; C016101:shikonin; D003094:Collagen