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

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)381-393
Number of pages13
JournalAmerican Journal of Pathology
Volume167
Issue number2
Publication statusPublished - 2005 Aug
Externally publishedYes

Fingerprint

Epithelial-Mesenchymal Transition
Catenins
Epithelial Cells
Air
Wnt Signaling Pathway
Stem Cells
Keratin-3
Limbus Corneae
Feeder Cells
Corneal Epithelium
Intercellular Junctions
Conjunctiva
Collagenases
Cadherins
Cornea
Regeneration
Cytoplasm
Fibrosis
Fibroblasts
Health

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Kawakita, T., Espana, E. M., He, H., Li, W., Liu, C. Y., & Tseng, S. G. G. (2005). Intrastromal invasion by limbal epithelial cells is mediated by epithelial-mesenchymal transition activated by air exposure. American Journal of Pathology, 167(2), 381-393.

Intrastromal invasion by limbal epithelial cells is mediated by epithelial-mesenchymal transition activated by air exposure. / Kawakita, Tetsuya; Espana, Edgar M.; He, Hua; Li, Wei; Liu, Chia Yiang; Tseng, Scheffer G G.

In: American Journal of Pathology, Vol. 167, No. 2, 08.2005, p. 381-393.

Research output: Contribution to journalArticle

Kawakita, Tetsuya ; Espana, Edgar M. ; He, Hua ; Li, Wei ; Liu, Chia Yiang ; Tseng, Scheffer G G. / Intrastromal invasion by limbal epithelial cells is mediated by epithelial-mesenchymal transition activated by air exposure. In: American Journal of Pathology. 2005 ; Vol. 167, No. 2. pp. 381-393.
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