Functional Role of Lacrimal Gland Fibroblasts in a Mouse Model of Chronic Graft-Versus-Host Disease

Mio Yamane, Yoko Ogawa, Shin Mukai, Saori Yaguchi, Hajime Kamijuku, Takaaki Inaba, Kazuki Asai, Satoru Morikawa, Yutaka Kawakami, Shigeto Shimmura, Kazuo Tsubota

Research output: Contribution to journalArticle

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Abstract

PURPOSE: This study aimed to clarify the mechanisms and assess the characteristics of the chronic graft-versus-host disease (cGVHD) fibrosis in the lacrimal gland (LG) of mice.

METHODS: Histopathology of LG tissues was examined by immunohistochemistry and electron microscopy. Cultured fibroblasts derived from the LG were analyzed by phase-contrast microscopy, immunocytochemistry, flow cytometry, proliferation assay, and invasion and migration assays.

RESULTS: Cultured murine LG fibroblasts in cGVHD were spindle-shaped and relatively small, whereas those from syngeneic controls were polygon-shaped and relatively large. Flow cytometric analysis showed that the LG fibroblasts in cGVHD had elevated HSP47 levels. The LG fibroblasts in cGVHD also showed increased expression of major histocompatibility complex class II. Furthermore, the proportion of Sca-1PDGFR-α cells among the LG fibroblasts in cGVHD was considerably increased compared with controls. Cell counting kit-8 assays demonstrated that the LG fibroblasts in cGVHD were highly proliferative, and cell invasion assays indicated that they were highly invasive with high migration ability.

CONCLUSIONS: LG fibroblasts in cGVHD can be aberrantly activated, thereby eliciting fibrosis by producing excessive extracellular matrix, leading to LG dysfunction in mice.

Original languageEnglish
Pages (from-to)102-108
Number of pages7
JournalCornea
Volume37
Issue number1
DOIs
Publication statusPublished - 2018 Jan 1

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Lacrimal Apparatus
Graft vs Host Disease
Fibroblasts
Fibrosis
Immunohistochemistry
Phase-Contrast Microscopy
Major Histocompatibility Complex
Extracellular Matrix
Electron Microscopy
Flow Cytometry

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Functional Role of Lacrimal Gland Fibroblasts in a Mouse Model of Chronic Graft-Versus-Host Disease. / Yamane, Mio; Ogawa, Yoko; Mukai, Shin; Yaguchi, Saori; Kamijuku, Hajime; Inaba, Takaaki; Asai, Kazuki; Morikawa, Satoru; Kawakami, Yutaka; Shimmura, Shigeto; Tsubota, Kazuo.

In: Cornea, Vol. 37, No. 1, 01.01.2018, p. 102-108.

Research output: Contribution to journalArticle

Yamane, M, Ogawa, Y, Mukai, S, Yaguchi, S, Kamijuku, H, Inaba, T, Asai, K, Morikawa, S, Kawakami, Y, Shimmura, S & Tsubota, K 2018, 'Functional Role of Lacrimal Gland Fibroblasts in a Mouse Model of Chronic Graft-Versus-Host Disease', Cornea, vol. 37, no. 1, pp. 102-108. https://doi.org/10.1097/ICO.0000000000001411
Yamane, Mio ; Ogawa, Yoko ; Mukai, Shin ; Yaguchi, Saori ; Kamijuku, Hajime ; Inaba, Takaaki ; Asai, Kazuki ; Morikawa, Satoru ; Kawakami, Yutaka ; Shimmura, Shigeto ; Tsubota, Kazuo. / Functional Role of Lacrimal Gland Fibroblasts in a Mouse Model of Chronic Graft-Versus-Host Disease. In: Cornea. 2018 ; Vol. 37, No. 1. pp. 102-108.
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AU - Kamijuku, Hajime

AU - Inaba, Takaaki

AU - Asai, Kazuki

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AB - PURPOSE: This study aimed to clarify the mechanisms and assess the characteristics of the chronic graft-versus-host disease (cGVHD) fibrosis in the lacrimal gland (LG) of mice.METHODS: Histopathology of LG tissues was examined by immunohistochemistry and electron microscopy. Cultured fibroblasts derived from the LG were analyzed by phase-contrast microscopy, immunocytochemistry, flow cytometry, proliferation assay, and invasion and migration assays.RESULTS: Cultured murine LG fibroblasts in cGVHD were spindle-shaped and relatively small, whereas those from syngeneic controls were polygon-shaped and relatively large. Flow cytometric analysis showed that the LG fibroblasts in cGVHD had elevated HSP47 levels. The LG fibroblasts in cGVHD also showed increased expression of major histocompatibility complex class II. Furthermore, the proportion of Sca-1PDGFR-α cells among the LG fibroblasts in cGVHD was considerably increased compared with controls. Cell counting kit-8 assays demonstrated that the LG fibroblasts in cGVHD were highly proliferative, and cell invasion assays indicated that they were highly invasive with high migration ability.CONCLUSIONS: LG fibroblasts in cGVHD can be aberrantly activated, thereby eliciting fibrosis by producing excessive extracellular matrix, leading to LG dysfunction in mice.

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