Β-catenin activation and epithelial-mesenchymal transition in the pathogenesis of pterygium

• Published in: Investigative ophthalmology & visual science 2007-04, Vol.48 (4), p.1511-1517
• Main Authors: KATO, Naoko, SHIMMURA, Shigeto, KAWAKITA, Tetsuya, MIYASHITA, Hideyuki, OGAWA, Yoko, YOSHIDA, Satoru, HIGA, Kazunari, OKANO, Hideyuki, TSUBOTA, Kazuo
• Format: Article
• Language: English
• Subjects: Actins - metabolism; beta Catenin - metabolism; Biological and medical sciences; Cadherins - metabolism; Diseases of eyelid, conjunctiva and lacrimal tracts; Epithelial Cells - metabolism; Epithelial Cells - pathology; Eye and associated structures. Visual pathways and centers. Vision; Fibroblasts - metabolism; Fibroblasts - pathology; Fibrosis; Fluorescent Antibody Technique, Indirect; Fundamental and applied biological sciences. Psychology; Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) - genetics; Humans; Immunoenzyme Techniques; Keratin-14 - metabolism; Limbus Corneae - pathology; Lymphoid Enhancer-Binding Factor 1 - metabolism; Matrix Metalloproteinase 7 - genetics; Medical sciences; Ophthalmology; Pterygium - etiology; Pterygium - metabolism; Pterygium - pathology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Snail Family Transcription Factors; Transcription Factors - metabolism; Vertebrates: nervous system and sense organs; Vimentin - metabolism
• ISSN: 0146-0404; 1552-5783; 1552-5783
• DOI: 10.1167/iovs.06-1060

To investigate whether beta-catenin activation and epithelial-mesenchymal transition (EMT) is involved in the pathogenesis of pterygium. 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. 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. EMT of basal epithelial cells may play a key role in the pathogenesis of pterygium.