title: Response of lens epithelial cells to injury: role of lumican in epithelial-mesenchymal transition.
abstract: OBJECTIVE
  Lens epithelial cells (LECs) undergo epithelial-mesenchcymal transition (EMT) after injury and transform into myofibroblasts positive for alpha-smooth muscle actin (alphaSMA), an established marker of this process. Lumican is a keratan sulfate proteoglycan core protein. This study was conducted to examine whether human and mouse LECs express lumican after injury. To determine whether lumican may modulate EMT of LECs in response to injury or to exposure to transforming growth factor-beta2 (TGFbeta2), alphaSMA expression by the LECs was examined in lumican (Lum)-knockout mice in vivo and in organ culture.
  
  
  METHODS
  Human postoperative capsular specimens and healing, injured mouse lenses at various intervals were immunostained for lumican or alphaSMA. alphaSMA was also immunolocalized in healing, injured lenses of Lum-knockout mice. Finally, expression of lumican and alphaSMA was examined in lenses of Lum-knockout mice incubated with TGFbeta2.
  
  
  RESULTS
  Lumican was immunolocalized in matrix in human postoperative capsular opacification. Lumican and alphaSMA were upregulated in mouse LECs from 8 hours and day 5 after an injury, respectively. LECs accumulated adjacent to the capsular break were of epithelial shape in Lum(-/-) mice and fibroblast-like in Lum(+/-) mice during healing. alphaSMA expression by LECs was significantly delayed in Lum(-/-) mice, indicating that lumican may modulate injury-induced EMT in LECs. TGFbeta2-induced EMT appeared to be suppressed in organ-cultured lenses of Lum(-/-) mice compared with those of Lum(+/+) mice.
  
  
  CONCLUSIONS
  Human capsular opacification contains lumican, and mouse LECs upregulate lumican and alphaSMA in response to injury. Loss of lumican perturbs EMT of mouse LECs.
authors.affiliation: Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan. shizuya@wakayama-med.ac.jp
authors.forename: Shizuya
authors.initials: S
authors.lastname: Saika
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Sai-ichi
authors.initials: S
authors.lastname: Tanaka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Iku
authors.initials: I
authors.lastname: Ishida
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Ohnishi
authors.forename: Akira
authors.initials: A
authors.lastname: Ooshima
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Ishiwata
authors.forename: Goro
authors.initials: G
authors.lastname: Asano
authors.forename: Tai-ichiro
authors.initials: T
authors.lastname: Chikama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shiraishi
authors.forename: Chia-Yang
authors.initials: CY
authors.lastname: Liu
authors.forename: Candace W-C
authors.initials: CW
authors.lastname: Kao
authors.forename: Winston W-Y
authors.initials: WW
authors.lastname: Kao
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002386:Cataract / Q000378:metabolism* / Q000473:pathology; D002387:Cataract Extraction; D011508:Chondroitin Sulfate Proteoglycans / Q000502:physiology*; D024042:Collagen Type I / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D015807:Eye Injuries, Penetrating / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005347:Fibroblasts; D006801:Humans; D007124:Immunoenzyme Techniques; D007632:Keratan Sulfate / Q000502:physiology*; D007903:Lens Capsule, Crystalline / Q000293:injuries* / Q000473:pathology; D000071234:Lumican; D008297:Male; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009924:Organ Culture Techniques; D011183:Postoperative Complications / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053781:Transforming Growth Factor beta2; D015854:Up-Regulation; D014945:Wound Healing / Q000502:physiology
chemical_list: D000199:Actins; D011508:Chondroitin Sulfate Proteoglycans; D024042:Collagen Type I; C000604306:LUM protein, human; C000604307:Lum protein, mouse; D000071234:Lumican; C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D007632:Keratan Sulfate