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

Research output: Contribution to journalArticle

48 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2126-2135
Number of pages10
JournalJournal of Investigative Dermatology
Volume129
Issue number9
DOIs
Publication statusPublished - 01-01-2009

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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

Cite this

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. In: Journal of Investigative Dermatology. 2009 ; Vol. 129, No. 9. pp. 2126-2135.
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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, vol. 129, no. 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.

In: Journal of Investigative Dermatology, Vol. 129, No. 9, 01.01.2009, p. 2126-2135.

Research output: Contribution to journalArticle

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AU - Sugiura, Kazumitsu

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AU - Tomita, Yasushi

AU - Usukura, Jiro

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