title: Silibinin inhibits myofibroblast transdifferentiation in human tenon fibroblasts and reduces fibrosis in a rabbit trabeculectomy model.
abstract: OBJECTIVE
  To investigate the effect of silibinin in myofibroblast transdifferentiation and in animal trabeculectomy models.
  
  
  METHODS
  The effect of silibinin on the expression of α-smooth muscle actin (α-SMA) and vimentin in response to transforming growth factor-β1 (TGF-β1) was determined in human tenon fibroblasts (HTFs). Cell migration and collagen contraction arrays were used to demonstrate the functionality of silibinin-modulated HTFs. ELISA analysis was used to determine the effect of silibinin on the release of type 1 collagen and connective tissue growth factor (CTGF). The effect of silibinin on the activation of the TGF-β receptor-related pathway was evaluated by Western blotting. A rabbit model of trabeculectomy was established to assess the effect of silibinin in vivo.
  
  
  RESULTS
  TGF-β1 elevated the expression of α-SMA and vimentin in HTFs; this elevation was inhibited by silibinin. TGF-β1 increased cell migration and collagen contraction of HTFs, which were also suppressed by silibinin. The production of both CTGF and type 1 collagen in TGF-β1-treated HTFs was inhibited by silibinin. The effects of silibinin on TGF-β1-stimulated HTFs were mediated via the down-regulation of TGF-β receptor-related SMAD signalling pathways. In the rabbit model of trabeculectomy, silibinin increased the period of decreasing intraocular pressure after trabeculectomy and reduced the production of collagen and α-SMA at the site of blebs in vivo.
  
  
  CONCLUSIONS
  Silibinin inhibited the TGF-β receptor-related signalling pathway in TGF-β-treated HTFs and several of the downstream events associated with myofibroblast transdifferentiation. Silibinin also improved the outcome of trabeculectomies by reducing the fibrotic response in the bleb tissue in vivo.
authors.affiliation: Graduate Institute of Medical Science, National Defense Medical Center, Taipei, TaiwanDepartment of Ophthalmology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yi-Hao
authors.initials: YH
authors.lastname: Chen
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Liang
authors.forename: Ching-Long
authors.initials: CL
authors.lastname: Chen
authors.forename: Jiann-Torng
authors.initials: JT
authors.lastname: Chen
authors.forename: Yun-Hsiang
authors.initials: YH
authors.lastname: Chang
authors.forename: Da-Wen
authors.initials: DW
authors.lastname: Lu
authors.forename: Ke-Hung
authors.initials: KH
authors.lastname: Chien
authors.forename: Ming-Cheng
authors.initials: MC
authors.lastname: Tai
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D054338:Cell Transdifferentiation / Q000187:drug effects*; D024042:Collagen Type I / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005355:Fibrosis / Q000517:prevention & control; D006801:Humans; D058628:Myofibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011817:Rabbits; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D058475:Tenon Capsule / Q000166:cytology*; D014129:Trabecular Meshwork / Q000473:pathology; D014130:Trabeculectomy; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014746:Vimentin / Q000378:metabolism
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D000975:Antioxidants; D024042:Collagen Type I; D018125:Receptors, Transforming Growth Factor beta; D012838:Silymarin; D053773:Transforming Growth Factor beta1; D014746:Vimentin; D055513:Connective Tissue Growth Factor; D000077385:Silybin
keywords: TGF-β; human tenon fibroblast; silibinin; trabeculectomy