TY - JOUR
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
N1 - Funding Information:
This work was supported by a Grant-in-Aid for Scientific Research, (C) 20591319 (K.S.), from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
PY - 2009/9
Y1 - 2009/9
N2 - 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.
AB - 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.
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U2 - 10.1038/jid.2009.51
DO - 10.1038/jid.2009.51
M3 - Article
C2 - 19282840
AN - SCOPUS:84940363675
SN - 0022-202X
VL - 129
SP - 2126
EP - 2135
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 9
ER -