title: Upregulation of bone morphogenetic protein-1/mammalian tolloid and procollagen C-proteinase enhancer-1 in corneal scarring.
abstract: OBJECTIVE
  To characterize the expression of the bone morphogenetic protein-1 (BMP-1)/tolloid-like proteinases (collectively called BTPs), which include BMP-1, mammalian tolloid (mTLD), and mammalian tolloid-like 1 (mTLL-1) and 2 (mTLL-2), as well as the associated proteins procollagen C-proteinase enhancers (PCPE-1 and -2), in corneal scarring.
  
  
  METHODS
  Using a mouse full-thickness corneal excision model, wound healing was followed for up to 28 days by transmission electron microscopy, immunohistology (BMP-1/mTLD and PCPE-1), and quantitative PCR (Q-PCR: collagen III, BMP-1/mTLD, mTLL-1, mTLL-2, PCPE-1, PCPE-2). Bone morphogenetic protein-1/mTLD and PCPE-1 were also immunolocalized in cases of human corneal scarring following injuries.
  
  
  RESULTS
  In the mouse model, throughout the follow-up period, there was a large increase in collagen III mRNA expression in the stroma. By transmission electron microscopy, there was marked cellular infiltration into the wound as well as disorganization of collagen fibrils, but no significant difference in fibril diameter. In control corneas, by Q-PCR, BMP-1/mTLD showed the highest expression, compared to low levels of mTLL-1 and undetectable levels of mTLL-2, in both epithelium and stroma. Following wounding, both BMP-1/mTLD and PCPE-1 mRNA and protein increased, while PCPE-2 mRNA decreased. Finally, by immunofluorescence, BMP-1/mTLD and PCPE-1 were strongly expressed in the scar region in both mouse and human corneas.
  
  
  CONCLUSIONS
  Bone morphogenetic protein-1/mTLD and PCPE-1 are upregulated in corneal scars. Both proteins may therefore contribute to the process of corneal scarring.
authors.affiliation: Equipe d'Accueil (EA) 4555, Université Toulouse III Paul Sabatier, Toulouse, France Centre Hospitalier Universitaire (CHU) Toulouse, Hôpital Purpan, Service d'Ophtalmologie, Toulouse, France.
authors.forename: Francois
authors.initials: F
authors.lastname: Malecaze
authors.affiliation: Equipe d'Accueil (EA) 4555, Université Toulouse III Paul Sabatier, Toulouse, France.
authors.forename: Dawiyat
authors.initials: D
authors.lastname: Massoudi
authors.affiliation: Equipe d'Accueil (EA) 4555, Université Toulouse III Paul Sabatier, Toulouse, France Centre Hospitalier Universitaire (CHU) Toulouse, Hôpital Purpan, Service d'Ophtalmologie, Toulouse, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Fournié
authors.affiliation: Equipe d'Accueil (EA) 4555, Université Toulouse III Paul Sabatier, Toulouse, France.
authors.forename: Cyrielle
authors.initials: C
authors.lastname: Tricoire
authors.affiliation: Equipe d'Accueil (EA) 4555, Université Toulouse III Paul Sabatier, Toulouse, France Centre Hospitalier Universitaire (CHU) Toulouse, Hôpital Purpan, Service d'Ophtalmologie, Toulouse, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Cassagne
authors.affiliation: Unité Mixte de Recherche (UMR) 5242 Centre National de la Recherche Scientifique (CNRS)/Ecole Normale Supérieure de Lyon/Université Lyon 1, Lyon, France.
authors.forename: Marilyne
authors.initials: M
authors.lastname: Malbouyres
authors.affiliation: UMR 5305 CNRS/Université Lyon 1, Lyon, France.
authors.forename: David J S
authors.initials: DJ
authors.lastname: Hulmes
authors.affiliation: UMR 5305 CNRS/Université Lyon 1, Lyon, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Moali
authors.affiliation: Equipe d'Accueil (EA) 4555, Université Toulouse III Paul Sabatier, Toulouse, France Centre Hospitalier Universitaire (CHU) Toulouse, Hôpital Purpan, Service d'Ophtalmologie, Toulouse, France.
authors.forename: Stephane D
authors.initials: SD
authors.lastname: Galiacy
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D055395:Bone Morphogenetic Protein 1 / Q000096:biosynthesis / Q000235:genetics*; D002921:Cicatrix / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003315:Cornea / Q000378:metabolism* / Q000648:ultrastructure; D065306:Corneal Injuries / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D014945:Wound Healing; D055815:Young Adult
chemical_list: D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C108243:Pcolce protein, mouse; D012333:RNA, Messenger; D055395:Bone Morphogenetic Protein 1
keywords: BMP1; PCPE1; collagen; corneal wound healing