Epithelial mesenchymal transition in human ocular chronic graft-versus-host disease

Yoko Ogawa, Shigeto Shimmura, Tetsuya Kawakita, Satoru Yoshida, Yutaka Kawakami, Kazuo Tsubota

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Chronic graft-versus-host disease (cGVHD) of the ocular surface and lacrimal gland is a vision-threatening condition that occurs after allogeneic bone marrow transplantation. In this study, we used immunohistochemistry and electron microscopy to investigate whether epithelial mesenchymal transition (EMT) contributed to the pathogenesis of ocular cGVHD. We detected down-regulation of E-cadherin and translocation of β-catenin from the intercellular junction to the cytoplasm and nucleus of cGVHD conjunctival basal epithelia and lacrimal gland myoepithelia. Notable findings included expression of Snail, an inducer of EMT, in the nucleus of ocular cGVHD epithelia. The fibrosis markers heat shock protein 47, α-smooth muscle actin, and fibroblast specific protein-1 were overexpressed in ocular cGVHD epithelia. In addition, p63, a marker of conjunctival basal epithelia, was observed in the nuclei of subconjunctival cells beneath disrupted basal lamina. Disrupted basal lamina and the presence of altered collagen bundles were observed in the cytoplasm and beneath cGVHD epithelia. In contrast, these observations were rarely observed in the normal conjunctiva and in Sjögren's syndrome lacrimal gland epithelia. These findings together indicate that ocular cGVHD epithelia gain the mesenchymal phenotype and the capacity to migrate into the subepithelial stroma. Our findings suggest that EMT may be partially responsible for the conjunctival and lacrimal gland fibrosis found in patients with cGVHD.

Original languageEnglish
Pages (from-to)2372-2381
Number of pages10
JournalAmerican Journal of Pathology
Volume175
Issue number6
DOIs
Publication statusPublished - 2009

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Epithelial-Mesenchymal Transition
Graft vs Host Disease
Epithelium
Lacrimal Apparatus
Basement Membrane
HSP47 Heat-Shock Proteins
Cytoplasm
Fibrosis
Catenins
Intercellular Junctions
Conjunctiva
Homologous Transplantation
Cadherins
Cell Nucleus
Bone Marrow Transplantation
Smooth Muscle
Actins
Electron Microscopy
Collagen
Down-Regulation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Epithelial mesenchymal transition in human ocular chronic graft-versus-host disease. / Ogawa, Yoko; Shimmura, Shigeto; Kawakita, Tetsuya; Yoshida, Satoru; Kawakami, Yutaka; Tsubota, Kazuo.

In: American Journal of Pathology, Vol. 175, No. 6, 2009, p. 2372-2381.

Research output: Contribution to journalArticle

Ogawa, Yoko ; Shimmura, Shigeto ; Kawakita, Tetsuya ; Yoshida, Satoru ; Kawakami, Yutaka ; Tsubota, Kazuo. / Epithelial mesenchymal transition in human ocular chronic graft-versus-host disease. In: American Journal of Pathology. 2009 ; Vol. 175, No. 6. pp. 2372-2381.
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