The unfolded protein response is activated in differentiating epidermal keratinocytes

Kazumitsu Sugiura, Yoshinao Muro, Kyoko Futamura, Kenji Matsumoto, Noriko Hashimoto, Yuji Nishizawa, Tetsuro Nagasaka, Hirohisa Saito, Yasushi Tomita, Jiro Usukura

研究成果: Article

48 引用 (Scopus)

抄録

The unfolded protein response (UPR), which is induced by stress to the endoplasmic reticulum (ER), is involved in the functional alteration of certain cells, such as the differentiation of B cells to plasma cells. The aim of this study is to determine whether the UPR is activated during epidermal keratinocyte (KC) differentiation. Here, we show that the expression of the UPR-induced proteins Bip/GRP78 and HRD1 was increased in cells in the supra-basal layers of normal human epidermis that contain KCs undergoing differentiation as well as in skin-equivalent cultured KCs. However, Bip/GRP78 and HRD1 were poorly expressed in proliferating KCs in squamous cell carcinoma and psoriasis vulgaris tissues. The epidermal growth factor receptor tyrosine kinase inhibitor, PD153035, which induces KC differentiation, upregulated UPR-induced marker mRNAs and proteins. Furthermore, microarray analyses and quantitative PCR revealed that ER stress-inducing reagents, tunicamycin (TU), thapsigargin, and brefeldin A, altered the expression of genes essential for human epidermal KC differentiation, including C/EBPΒ, KLF4, and ABCA12 in vitro. However, ABCA12 and KLF4 mRNA did not increase with TU treatment after siRNA-mediated knockdown of XBP-1. Taken together, our findings strongly suggest that the UPR is activated during normal epidermal KC differentiation and induces C/EBPΒ, KLF4, and ABCA12 mRNAs.

元の言語English
ページ(範囲)2126-2135
ページ数10
ジャーナルJournal of Investigative Dermatology
129
発行部数9
DOI
出版物ステータスPublished - 09-2009

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Unfolded Protein Response
Keratinocytes
Tunicamycin
Endoplasmic Reticulum Stress
Proteins
Messenger RNA
Brefeldin A
Thapsigargin
Essential Genes
Microarray Analysis
Plasma Cells
Psoriasis
Epidermal Growth Factor Receptor
Epidermis
Protein-Tyrosine Kinases
Small Interfering RNA
Squamous Cell Carcinoma
B-Lymphocytes
Microarrays
Gene Expression

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

これを引用

Sugiura, K., Muro, Y., Futamura, K., Matsumoto, K., Hashimoto, N., Nishizawa, Y., ... Usukura, J. (2009). The unfolded protein response is activated in differentiating epidermal keratinocytes. Journal of Investigative Dermatology, 129(9), 2126-2135. https://doi.org/10.1038/jid.2009.51
Sugiura, Kazumitsu ; Muro, Yoshinao ; Futamura, Kyoko ; Matsumoto, Kenji ; Hashimoto, Noriko ; Nishizawa, Yuji ; Nagasaka, Tetsuro ; Saito, Hirohisa ; Tomita, Yasushi ; Usukura, Jiro. / The unfolded protein response is activated in differentiating epidermal keratinocytes. :: Journal of Investigative Dermatology. 2009 ; 巻 129, 番号 9. pp. 2126-2135.
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abstract = "The unfolded protein response (UPR), which is induced by stress to the endoplasmic reticulum (ER), is involved in the functional alteration of certain cells, such as the differentiation of B cells to plasma cells. The aim of this study is to determine whether the UPR is activated during epidermal keratinocyte (KC) differentiation. Here, we show that the expression of the UPR-induced proteins Bip/GRP78 and HRD1 was increased in cells in the supra-basal layers of normal human epidermis that contain KCs undergoing differentiation as well as in skin-equivalent cultured KCs. However, Bip/GRP78 and HRD1 were poorly expressed in proliferating KCs in squamous cell carcinoma and psoriasis vulgaris tissues. The epidermal growth factor receptor tyrosine kinase inhibitor, PD153035, which induces KC differentiation, upregulated UPR-induced marker mRNAs and proteins. Furthermore, microarray analyses and quantitative PCR revealed that ER stress-inducing reagents, tunicamycin (TU), thapsigargin, and brefeldin A, altered the expression of genes essential for human epidermal KC differentiation, including C/EBPΒ, KLF4, and ABCA12 in vitro. However, ABCA12 and KLF4 mRNA did not increase with TU treatment after siRNA-mediated knockdown of XBP-1. Taken together, our findings strongly suggest that the UPR is activated during normal epidermal KC differentiation and induces C/EBPΒ, KLF4, and ABCA12 mRNAs.",
author = "Kazumitsu Sugiura and Yoshinao Muro and Kyoko Futamura and Kenji Matsumoto and Noriko Hashimoto and Yuji Nishizawa and Tetsuro Nagasaka and Hirohisa Saito and Yasushi Tomita and Jiro Usukura",
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Sugiura, K, Muro, Y, Futamura, K, Matsumoto, K, Hashimoto, N, Nishizawa, Y, Nagasaka, T, Saito, H, Tomita, Y & Usukura, J 2009, 'The unfolded protein response is activated in differentiating epidermal keratinocytes', Journal of Investigative Dermatology, 巻. 129, 番号 9, pp. 2126-2135. https://doi.org/10.1038/jid.2009.51

The unfolded protein response is activated in differentiating epidermal keratinocytes. / Sugiura, Kazumitsu; Muro, Yoshinao; Futamura, Kyoko; Matsumoto, Kenji; Hashimoto, Noriko; Nishizawa, Yuji; Nagasaka, Tetsuro; Saito, Hirohisa; Tomita, Yasushi; Usukura, Jiro.

:: Journal of Investigative Dermatology, 巻 129, 番号 9, 09.2009, p. 2126-2135.

研究成果: Article

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T1 - The unfolded protein response is activated in differentiating epidermal keratinocytes

AU - Sugiura, Kazumitsu

AU - Muro, Yoshinao

AU - Futamura, Kyoko

AU - Matsumoto, Kenji

AU - Hashimoto, Noriko

AU - Nishizawa, Yuji

AU - Nagasaka, Tetsuro

AU - Saito, Hirohisa

AU - Tomita, Yasushi

AU - Usukura, Jiro

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