Serum affects keratinization and tight junctions in three-dimensional cultures of the mouse keratinocyte cell line COCA through retinoic acid receptor-mediated signaling

Akane Ozaki, Takahito Otani, Norio Kitagawa, Kayoko Ogata, Hiroshi Iida, Hiroshi Kojima, Tetsuichiro Inai

研究成果: ジャーナルへの寄稿記事

2 引用 (Scopus)

抄録

Vitamin A, which is found in serum, is known to affect keratinocyte proliferation, epidermal differentiation, and keratinization. In mice, stratified epithelia in the oral cavity, esophagus, and forestomach are keratinized; however, these epithelia are not keratinized in humans. Several studies have reported that three-dimensional (3D) cultures of human keratinocytes in serum-containing medium could form keratinized epithelia. Here, we evaluated the effects of serum on the morphology, expression, and localization of differentiation markers and tight junction proteins, and paracellular permeability in 3D cultures of mouse keratinocytes. We found that only 0.1% calcium-depleted serum inhibited keratinization and induced a change in the expression of differentiation marker proteins from loricrin to keratin 4; the inhibition of retinoic acid receptor-mediated signaling reversed these changes. Furthermore, the serum reduced claudin-1 protein expression and prevented its localization at occludin-positive spots on the surface of 3D cultures. On the other hand, the serum increased the protein expression of claudin-4, occludin, zonula occludens-1, and E-cadherin. These changes may contribute to the reduction of the transepithelial electrical resistance by approximately half. In conclusion, mouse keratinocytes derived from the epidermis formed non-keratinized structures in 3D cultures in response to vitamin A in serum. The results suggest that retinoic acid receptor-mediated signaling may be inhibited in the mouse epithelia in the oral cavity, esophagus, and forestomach as well as the epidermis, leading to the keratinization of these epithelia.

元の言語英語
ページ(範囲)315-326
ページ数12
ジャーナルHistochemistry and Cell Biology
151
発行部数4
DOI
出版物ステータス出版済み - 4 8 2019

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Retinoic Acid Receptors
Tight Junctions
Keratinocytes
Epithelium
Cell Line
Serum
Occludin
Differentiation Antigens
Vitamin A
Epidermis
Esophagus
Mouth
Keratin-4
Claudin-4
Claudins
Claudin-1
Tight Junction Proteins
Cadherins
Electric Impedance
Blood Proteins

All Science Journal Classification (ASJC) codes

  • Histology
  • Molecular Biology
  • Medical Laboratory Technology
  • Cell Biology

これを引用

Serum affects keratinization and tight junctions in three-dimensional cultures of the mouse keratinocyte cell line COCA through retinoic acid receptor-mediated signaling. / Ozaki, Akane; Otani, Takahito; Kitagawa, Norio; Ogata, Kayoko; Iida, Hiroshi; Kojima, Hiroshi; Inai, Tetsuichiro.

:: Histochemistry and Cell Biology, 巻 151, 番号 4, 08.04.2019, p. 315-326.

研究成果: ジャーナルへの寄稿記事

Ozaki, Akane ; Otani, Takahito ; Kitagawa, Norio ; Ogata, Kayoko ; Iida, Hiroshi ; Kojima, Hiroshi ; Inai, Tetsuichiro. / Serum affects keratinization and tight junctions in three-dimensional cultures of the mouse keratinocyte cell line COCA through retinoic acid receptor-mediated signaling. :: Histochemistry and Cell Biology. 2019 ; 巻 151, 番号 4. pp. 315-326.
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abstract = "Vitamin A, which is found in serum, is known to affect keratinocyte proliferation, epidermal differentiation, and keratinization. In mice, stratified epithelia in the oral cavity, esophagus, and forestomach are keratinized; however, these epithelia are not keratinized in humans. Several studies have reported that three-dimensional (3D) cultures of human keratinocytes in serum-containing medium could form keratinized epithelia. Here, we evaluated the effects of serum on the morphology, expression, and localization of differentiation markers and tight junction proteins, and paracellular permeability in 3D cultures of mouse keratinocytes. We found that only 0.1{\%} calcium-depleted serum inhibited keratinization and induced a change in the expression of differentiation marker proteins from loricrin to keratin 4; the inhibition of retinoic acid receptor-mediated signaling reversed these changes. Furthermore, the serum reduced claudin-1 protein expression and prevented its localization at occludin-positive spots on the surface of 3D cultures. On the other hand, the serum increased the protein expression of claudin-4, occludin, zonula occludens-1, and E-cadherin. These changes may contribute to the reduction of the transepithelial electrical resistance by approximately half. In conclusion, mouse keratinocytes derived from the epidermis formed non-keratinized structures in 3D cultures in response to vitamin A in serum. The results suggest that retinoic acid receptor-mediated signaling may be inhibited in the mouse epithelia in the oral cavity, esophagus, and forestomach as well as the epidermis, leading to the keratinization of these epithelia.",
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AU - Otani, Takahito

AU - Kitagawa, Norio

AU - Ogata, Kayoko

AU - Iida, Hiroshi

AU - Kojima, Hiroshi

AU - Inai, Tetsuichiro

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