Beta-catenin activation and epithelial-mesenchymal transition in the pathogenesis of pterygium.
OBJECTIVE
To investigate whether beta-catenin activation and epithelial-mesenchymal transition (EMT) is involved in the pathogenesis of pterygium.


METHODS
beta-Catenin and E-cadherin expression were examined in surgically excised tissue and eye bank corneas with intact pterygium. Snail and Slug, the transcriptional repressors of E-cadherin, and matrix metalloproteinase (MMP)-7, a down-stream gene regulated by beta-catenin were also investigated. Epithelial cells undergoing EMT-like changes were identified by double immunostaining for alpha-smooth muscle actin (SMA)/vimentin and cytokeratin 14. Transmission electron microscopy was used to examine the ultrastructure of the pterygial head.


RESULTS
Histopathology showed aberrant fibrotic proliferation beneath the pterygium epithelium, with epithelial processes extending into the stroma. Transmission electron microscopy revealed the dissociation of epithelial cells, which were surrounded by activated fibroblast-like cells. Characteristic downregulation of E-cadherin and intranuclear accumulation of beta-catenin and lymphoid-enhancer-factor-1 in pterygial epithelium were also observed by immunohistochemistry. Of note, epithelial cells extending into the stroma were positive for both alpha-SMA/vimentin and cytokeratin 14. Snail and Slug were immunopositive in the nuclei of pterygial epithelial cells, but not in normal corneal epithelial cells.


CONCLUSIONS
EMT of basal epithelial cells may play a key role in the pathogenesis of pterygium.
Kato
Naoko
N
Department of Ophthalmology; Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Shimmura
Shigeto
S
Kawakita
Tetsuya
T
Miyashita
Hideyuki
H
Ogawa
Yoko
Y
Yoshida
Satoru
S
Higa
Kazunari
K
Okano
Hideyuki
H
Tsubota
Kazuo
K
D000199:Actins / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D005355:Fibrosis; D019084:Fluorescent Antibody Technique, Indirect; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000235:genetics; D006801:Humans; D007124:Immunoenzyme Techniques; D053547:Keratin-14 / Q000378:metabolism; D016850:Limbus Corneae / Q000473:pathology; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism; D020783:Matrix Metalloproteinase 7 / Q000235:genetics; D011625:Pterygium / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
D000199:Actins; D015820:Cadherins; D053547:Keratin-14; C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; D012333:RNA, Messenger; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D014746:Vimentin; D051176:beta Catenin; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7