Lack of plakoglobin impairs integrity and wound healing in corneal epithelium in mice

Masahide Kokado, Masayasu Miyajima, Yuka Okada, Kana Ichikawa, Osamu Yamanaka, Chia Yang Liu, Winston Whei Yang Kao, Weinian Shou, Shizuya Saika

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

We generated cornea-specific plakoglobin (Jup; junctional plakoglobin) knockout mice in order to investigate the function of plakoglobin on the maintenance of the homeostasis of corneal epithelium in mice. Cornea epithelium-specific conditional knockouts (JupCEΔ/CEΔ) (cKO) were obtained by breeding keratin12-Cre (Krt12-Cre) mice to Jup-floxed (Jupf/f) mice. Light and transmission electron microscopic and immunohistochemical analyses were carried out to determine consequence of the loss of plakoglobin on maintaining corneal epithelium integrity under mechanical stress, e.g., brushing and wound healing. Immunohistochemistry analysis demonstrated that, although Jup ablation did not affect BrdU incorporation, basal cell-like cells labeled for keratin 14 were ectopically present in the supra-basal layer in mutant corneal epithelium, suggestive of altered cell differentiation. Plakoglobin-deficient epithelium exhibits increased fragility against mechanical intervention when compared to wild-type controls under identical treatment. Closure of an epithelial defect was significantly delayed in JupCEΔ/CEΔ epithelium. Our findings indicate that the lack of plakoglobin significantly affects corneal epithelium differentiation, as well as its structural integrity. Plakoglobin is essential to the maintenance of the structure of the corneal epithelium and its wound healing.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalLaboratory Investigation
DOIs
StateAccepted/In press - May 25 2018

Fingerprint

gamma Catenin
Corneal Epithelium
Wound Healing
Epithelium
Cornea
Maintenance
Keratin-14
Mechanical Stress
Bromodeoxyuridine
Knockout Mice
Breeding
Cell Differentiation
Homeostasis
Immunohistochemistry
Electrons
Light

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Kokado, M., Miyajima, M., Okada, Y., Ichikawa, K., Yamanaka, O., Liu, C. Y., ... Saika, S. (Accepted/In press). Lack of plakoglobin impairs integrity and wound healing in corneal epithelium in mice. Laboratory Investigation, 1-9. https://doi.org/10.1038/s41374-018-0082-z

Lack of plakoglobin impairs integrity and wound healing in corneal epithelium in mice. / Kokado, Masahide; Miyajima, Masayasu; Okada, Yuka; Ichikawa, Kana; Yamanaka, Osamu; Liu, Chia Yang; Kao, Winston Whei Yang; Shou, Weinian; Saika, Shizuya.

In: Laboratory Investigation, 25.05.2018, p. 1-9.

Research output: Contribution to journalArticle

Kokado, M, Miyajima, M, Okada, Y, Ichikawa, K, Yamanaka, O, Liu, CY, Kao, WWY, Shou, W & Saika, S 2018, 'Lack of plakoglobin impairs integrity and wound healing in corneal epithelium in mice', Laboratory Investigation, pp. 1-9. https://doi.org/10.1038/s41374-018-0082-z
Kokado, Masahide ; Miyajima, Masayasu ; Okada, Yuka ; Ichikawa, Kana ; Yamanaka, Osamu ; Liu, Chia Yang ; Kao, Winston Whei Yang ; Shou, Weinian ; Saika, Shizuya. / Lack of plakoglobin impairs integrity and wound healing in corneal epithelium in mice. In: Laboratory Investigation. 2018 ; pp. 1-9.
@article{faa65bf336f140cfa31b9fa653b95a97,
title = "Lack of plakoglobin impairs integrity and wound healing in corneal epithelium in mice",
abstract = "We generated cornea-specific plakoglobin (Jup; junctional plakoglobin) knockout mice in order to investigate the function of plakoglobin on the maintenance of the homeostasis of corneal epithelium in mice. Cornea epithelium-specific conditional knockouts (JupCEΔ/CEΔ) (cKO) were obtained by breeding keratin12-Cre (Krt12-Cre) mice to Jup-floxed (Jupf/f) mice. Light and transmission electron microscopic and immunohistochemical analyses were carried out to determine consequence of the loss of plakoglobin on maintaining corneal epithelium integrity under mechanical stress, e.g., brushing and wound healing. Immunohistochemistry analysis demonstrated that, although Jup ablation did not affect BrdU incorporation, basal cell-like cells labeled for keratin 14 were ectopically present in the supra-basal layer in mutant corneal epithelium, suggestive of altered cell differentiation. Plakoglobin-deficient epithelium exhibits increased fragility against mechanical intervention when compared to wild-type controls under identical treatment. Closure of an epithelial defect was significantly delayed in JupCEΔ/CEΔ epithelium. Our findings indicate that the lack of plakoglobin significantly affects corneal epithelium differentiation, as well as its structural integrity. Plakoglobin is essential to the maintenance of the structure of the corneal epithelium and its wound healing.",
author = "Masahide Kokado and Masayasu Miyajima and Yuka Okada and Kana Ichikawa and Osamu Yamanaka and Liu, {Chia Yang} and Kao, {Winston Whei Yang} and Weinian Shou and Shizuya Saika",
year = "2018",
month = "5",
day = "25",
doi = "10.1038/s41374-018-0082-z",
language = "English (US)",
pages = "1--9",
journal = "Laboratory Investigation",
issn = "0023-6837",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Lack of plakoglobin impairs integrity and wound healing in corneal epithelium in mice

AU - Kokado, Masahide

AU - Miyajima, Masayasu

AU - Okada, Yuka

AU - Ichikawa, Kana

AU - Yamanaka, Osamu

AU - Liu, Chia Yang

AU - Kao, Winston Whei Yang

AU - Shou, Weinian

AU - Saika, Shizuya

PY - 2018/5/25

Y1 - 2018/5/25

N2 - We generated cornea-specific plakoglobin (Jup; junctional plakoglobin) knockout mice in order to investigate the function of plakoglobin on the maintenance of the homeostasis of corneal epithelium in mice. Cornea epithelium-specific conditional knockouts (JupCEΔ/CEΔ) (cKO) were obtained by breeding keratin12-Cre (Krt12-Cre) mice to Jup-floxed (Jupf/f) mice. Light and transmission electron microscopic and immunohistochemical analyses were carried out to determine consequence of the loss of plakoglobin on maintaining corneal epithelium integrity under mechanical stress, e.g., brushing and wound healing. Immunohistochemistry analysis demonstrated that, although Jup ablation did not affect BrdU incorporation, basal cell-like cells labeled for keratin 14 were ectopically present in the supra-basal layer in mutant corneal epithelium, suggestive of altered cell differentiation. Plakoglobin-deficient epithelium exhibits increased fragility against mechanical intervention when compared to wild-type controls under identical treatment. Closure of an epithelial defect was significantly delayed in JupCEΔ/CEΔ epithelium. Our findings indicate that the lack of plakoglobin significantly affects corneal epithelium differentiation, as well as its structural integrity. Plakoglobin is essential to the maintenance of the structure of the corneal epithelium and its wound healing.

AB - We generated cornea-specific plakoglobin (Jup; junctional plakoglobin) knockout mice in order to investigate the function of plakoglobin on the maintenance of the homeostasis of corneal epithelium in mice. Cornea epithelium-specific conditional knockouts (JupCEΔ/CEΔ) (cKO) were obtained by breeding keratin12-Cre (Krt12-Cre) mice to Jup-floxed (Jupf/f) mice. Light and transmission electron microscopic and immunohistochemical analyses were carried out to determine consequence of the loss of plakoglobin on maintaining corneal epithelium integrity under mechanical stress, e.g., brushing and wound healing. Immunohistochemistry analysis demonstrated that, although Jup ablation did not affect BrdU incorporation, basal cell-like cells labeled for keratin 14 were ectopically present in the supra-basal layer in mutant corneal epithelium, suggestive of altered cell differentiation. Plakoglobin-deficient epithelium exhibits increased fragility against mechanical intervention when compared to wild-type controls under identical treatment. Closure of an epithelial defect was significantly delayed in JupCEΔ/CEΔ epithelium. Our findings indicate that the lack of plakoglobin significantly affects corneal epithelium differentiation, as well as its structural integrity. Plakoglobin is essential to the maintenance of the structure of the corneal epithelium and its wound healing.

UR - http://www.scopus.com/inward/record.url?scp=85047443651&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85047443651&partnerID=8YFLogxK

U2 - 10.1038/s41374-018-0082-z

DO - 10.1038/s41374-018-0082-z

M3 - Article

SP - 1

EP - 9

JO - Laboratory Investigation

JF - Laboratory Investigation

SN - 0023-6837

ER -