title: NC1 long and NC3 short splice variants of type XII collagen are overexpressed during corneal scarring.
abstract: OBJECTIVE
  To investigate type XII collagen expression in corneal scars in vivo.
  
  
  METHODS
  Type XII collagen protein expression was evaluated by immunohistochemistry in human corneal scars and in a mouse model of corneal scarring at several time points (from day 7 to day 210) after full-thickness excision. Alternative splice variants of the NC3 and NC1 domains of type XII collagen were investigated in the mouse wound-healing model using RT-PCR.
  
  
  RESULTS
  Type XII collagen was overexpressed in human corneal scars in areas that were also positive for alpha-smooth muscle actin staining. In a mouse model of corneal wound injury we found that at 14 and 21 days postexcision, type XII collagen was largely concentrated in the subepithelial region of the cornea, especially in and near the wound bed. By 28 days postexcision, expression of type XII collagen decreased but remained higher than that in controls. NC3 short form is the main form expressed in the cornea during the wound-healing process. After injury, the NC1 long splice variant mRNA was the most highly overexpressed variant in the cornea, especially in the epithelium (×2.7, 3.72, and 5.57 at days 7, 14, and 21, respectively, P < 0.01 to 0.001 compared with uninjured samples). Corneal scars from a 7-month-old mouse revealed an overexpression of type XII collagen in the wound area similar to what we observed in human corneal scars.
  
  
  CONCLUSIONS
  Type XII collagen is overexpressed in permanent human and mouse corneal scars and could represent a new target to treat corneal scarring.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U563, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France.
authors.forename: Dawiyat
authors.initials: D
authors.lastname: Massoudi
authors.forename: François
authors.initials: F
authors.lastname: Malecaze
authors.forename: Vincent
authors.initials: V
authors.lastname: Soler
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Butterworth
authors.forename: Angélique
authors.initials: A
authors.lastname: Erraud
authors.forename: Pierre
authors.initials: P
authors.lastname: Fournié
authors.forename: Manuel
authors.initials: M
authors.lastname: Koch
authors.forename: Stéphane D
authors.initials: SD
authors.lastname: Galiacy
mesh_terms: D000328:Adult; D000368:Aged; D017398:Alternative Splicing; D000818:Animals; D002921:Cicatrix / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D024082:Collagen Type XII / Q000096:biosynthesis / Q000235:genetics*; D003315:Cornea / Q000378:metabolism; D003316:Corneal Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D065306:Corneal Injuries; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014945:Wound Healing; D055815:Young Adult
chemical_list: D024082:Collagen Type XII; D012333:RNA, Messenger