PMID- 31953037
OWN - NLM
STAT- MEDLINE
DCOM- 20200518
LR  - 20200518
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 190
IP  - 3
DP  - 2020 Mar
TI  - Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Regulates Epidermal 
      Keratinization under Psoriatic Skin Inflammation.
PG  - 577-585
LID - S0002-9440(20)30002-X [pii]
LID - 10.1016/j.ajpath.2019.10.022 [doi]
AB  - Psoriasis is an autoinflammatory/autoimmune skin disease and the epitome of an 
      exaggerated primary inflammatory response in the surface barrier tissue. Despite 
      the efficacy of dimethyl fumarate, an electrophilic drug for psoriasis 
      management, there is a paucity of mechanistic evidence in vivo. In response to 
      electrophiles, the Kelch-like erythroid cell-derived protein with cap-n-collar 
      homology-associated protein 1/nuclear factor erythroid 2-related factor 2 (NRF2) 
      system mediates a myriad of cytoprotective mechanisms, including the regulation 
      of excessive inflammatory response and epidermal differentiation. Because the 
      psoriasiform tissue reaction comprises neutrophil infiltration and parakeratotic 
      scaling, it is hypothesized that Nrf2 not only regulates inflammatory responses 
      but also maintains epidermal differentiation, a hallmark of epidermal 
      homeostasis. By using the imiquimod-induced cutaneous inflammation model, an 
      exaggerated inflammatory response and impaired epidermal differentiation in 
      Nrf2(-/-) mice was detected. Dimethyl fumarate treatment in Nrf2(+/+) mice 
      attenuated a psoriasiform tissue reaction and rescued epidermal differentiation, 
      which was not observed in Nrf2(-/-) mice. In accordance with the fact that 
      psoriasis plaques form well-demarcated parakeratotic lesions in association with 
      the psoriasiform tissue reaction, the lesional skin showed reduced expression 
      levels of NRF2 and its downstream target genes compared with nonlesional skin. In 
      conclusion, Nrf2 attenuates the psoriasiform tissue reaction and underscores the 
      mechanistic legitimacy of the electrophile-based approach for the management of 
      psoriasis.
CI  - Copyright (c) 2020 American Society for Investigative Pathology. Published by 
      Elsevier Inc. All rights reserved.
FAU - Ogawa, Tatsuya
AU  - Ogawa T
AD  - Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, 
      Japan.
FAU - Ishitsuka, Yosuke
AU  - Ishitsuka Y
AD  - Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, 
      Japan. Electronic address: yosuke.ishitsuka@md.tsukuba.ac.jp.
FAU - Inoue, Sae
AU  - Inoue S
AD  - Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, 
      Japan.
FAU - Nakamura, Yoshiyuki
AU  - Nakamura Y
AD  - Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, 
      Japan.
FAU - Saito, Akimasa
AU  - Saito A
AD  - Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, 
      Japan.
FAU - Okiyama, Naoko
AU  - Okiyama N
AD  - Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, 
      Japan.
FAU - Fujisawa, Yasuhiro
AU  - Fujisawa Y
AD  - Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, 
      Japan.
FAU - Furuta, Junichi
AU  - Furuta J
AD  - Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, 
      Japan.
FAU - Watanabe, Rei
AU  - Watanabe R
AD  - Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, 
      Japan.
FAU - Fujimoto, Manabu
AU  - Fujimoto M
AD  - Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, 
      Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200114
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nfe2l2 protein, mouse)
RN  - P1QW714R7M (Imiquimod)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Chimera
MH  - Epidermis/drug effects/pathology
MH  - Female
MH  - Homeostasis/drug effects
MH  - Humans
MH  - Imiquimod/*adverse effects
MH  - Immunohistochemistry
MH  - Inflammation/chemically induced/*pathology
MH  - Keratinocytes/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - NF-E2-Related Factor 2/genetics/*metabolism
MH  - Parakeratosis/chemically induced/*pathology
MH  - Psoriasis/chemically induced/*pathology
MH  - Skin/drug effects/pathology
EDAT- 2020/01/19 06:00
MHDA- 2020/05/19 06:00
CRDT- 2020/01/19 06:00
PHST- 2019/02/19 00:00 [received]
PHST- 2019/10/21 00:00 [revised]
PHST- 2019/10/29 00:00 [accepted]
PHST- 2020/01/19 06:00 [pubmed]
PHST- 2020/05/19 06:00 [medline]
PHST- 2020/01/19 06:00 [entrez]
AID - S0002-9440(20)30002-X [pii]
AID - 10.1016/j.ajpath.2019.10.022 [doi]
PST - ppublish
SO  - Am J Pathol. 2020 Mar;190(3):577-585. doi: 10.1016/j.ajpath.2019.10.022. Epub 
      2020 Jan 14.