title: Inhibition by all-trans-retinoic acid of transforming growth factor-β-induced collagen gel contraction mediated by human tenon fibroblasts.
abstract: OBJECTIVE
  Excessive wound contraction can lead to scar formation in the conjunctiva. The effects of all-trans-retinoic acid (ATRA) on the contractility of human Tenon fibroblasts (HTFs) cultured in three-dimensional (3D) collagen gels were investigated.
  
  
  METHODS
  Human Tenon fibroblasts were cultured in 3D gels of type I collagen and in the absence or presence of TGF-β, ATRA, or various inhibitors. Collagen gel contraction was evaluated by measurement of gel diameter. Phosphorylation of various signaling molecules was examined by immunoblot analysis. The formation of actin stress fibers and focal adhesions was detected by laser confocal microscopy.
  
  
  RESULTS
  All-trans-retinoic acid inhibited TGF-β-induced collagen gel contraction mediated by HTFs in a concentration- and time-dependent manner. The TGF-β-induced phosphorylation of focal adhesion kinase (FAK) and formation of stress fibers and focal adhesions in HTFs were attenuated by ATRA. All-trans-retinoic acid also inhibited the TGF-β-induced phosphorylation of the mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinase (ERK), p38, and c-Jun NH2-terminal kinase (JNK) as well as that of c-Jun and Smad2/3. Furthermore, TGF-β-induced collagen gel contraction was blocked by inhibitors of ERK, p38, or JNK signaling.
  
  
  CONCLUSIONS
  All-trans-retinoic acid inhibited TGF-β-induced collagen gel contraction mediated by HTFs, most likely by attenuating the formation of actin stress fibers and focal adhesions as well as signaling by MAPKs, c-Jun, and Smads. All-trans-retinoic acid may therefore prove effective for inhibition of conjunctival scarring through attenuation of the contractility of Tenon fibroblasts.
authors.affiliation: Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, Ube City, Yamaguchi, Japan Department of Ophthalmology, First Hospital of Jilin University, Jilin, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, Ube City, Yamaguchi, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kimura
authors.affiliation: Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, Ube City, Yamaguchi, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Orita
authors.affiliation: Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, Ube City, Yamaguchi, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Teranishi
authors.affiliation: Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, Ube City, Yamaguchi, Japan.
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Ophthalmology, Yamaguchi University Graduate School of Medicine, Ube City, Yamaguchi, Japan.
authors.forename: Koh-Hei
authors.initials: KH
authors.lastname: Sonoda
mesh_terms: D002478:Cells, Cultured; D002921:Cicatrix / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000737:chemistry / Q000187:drug effects; D003228:Conjunctiva / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D005131:Eye Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D021621:Imaging, Three-Dimensional; D015151:Immunoblotting; D008856:Microscopy, Fluorescence; D058475:Tenon Capsule / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D016212:Transforming Growth Factor beta; D014212:Tretinoin; D003094:Collagen
keywords: Tenon fibroblasts; all-trans-retinoic acid; transforming growth factor-β; wound healing