Intrastromal invasion by limbal epithelial cells is mediated by epithelial-mesenchymal transition activated by air exposure

Tetsuya Kawakita, Edgar M. Espana, Hua He, Wei Li, Chia Yiang Liu, Scheffer G.G. Tseng

研究成果: Article査読

72 被引用数 (Scopus)

抄録

Corneal epithelial stem cells are located in the basal layer of the limbus between the cornea and the conjunctiva. Regulation of these limbal epithelial progenitor cells by the stromal niche dictates corneal surface health. To further characterize this process, limbal explants were cultured at the air-fluid interface, termed air-lifting, to stimulate the niche. As compared to submerged cultures, air-lifting significantly promoted epithelial stratification, migration, proliferation, and iatrastromal invasion by limbal epithelial cells. Epithelial intrastromal invasion was noted when the limbal, but not corneal, epithelium was recombined with the limbal stroma containing live, but not dead, cells. Invading limbal basal cells displayed up-regulated nuclear expression of p63 and Ki67, down-regulated E-cadherin and cornea-specific keratin 3, and switched expression of β-catenin from intercellular junctions to the nucleus and cytoplasm, indicating the activation of the Wnt/β-catenin pathway. Invaded cells isolated by collagenase from the stroma of air-lifted, but not submerged, explants showed vivid clonal growth on 3T3 fibroblast feeder layers and complete epithelial-mesenchymal transition by expressing nuclear p63 and cytoplasmic S100A4. These findings collectively suggest that epithelial-mesenchymal transition via the Wnt/β-catenin pathway influences the fate of limbal epithelial cells, likely to be progenitor cells, between regeneration and fibrosis when the stromal niche is activated.

本文言語English
ページ(範囲)381-393
ページ数13
ジャーナルAmerican Journal of Pathology
167
2
DOI
出版ステータスPublished - 2005 8

ASJC Scopus subject areas

  • 病理学および法医学

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