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MTH1 Inhibitors for...
MTH1 Inhibitors for the Treatment of Psoriasis
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- Bivik Eding, Cecilia (author)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten
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- Köhler, Ines (author)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten,Region Östergötland, Hudkliniken i Östergötland
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- Verma, Deepti (author)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten
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- Sjögren, Florence (author)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten,Region Östergötland, Hudkliniken i Östergötland
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- Bamberg, Claudia (author)
- Vastervik Hosp, Sweden
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- Karsten, Stella (author)
- Karolinska Institutet
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- Pham, Therese (author)
- Karolinska Institutet
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- Scobie, Martin (author)
- Karolinska Institutet
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- Helleday, Thomas (author)
- Karolinska Institutet
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- Berglund, Ulrika Warpman (author)
- Karolinska Institutet
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- Enerbäck, Charlotta (author)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten,Region Östergötland, Hudkliniken i Östergötland
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(creator_code:org_t)
- ELSEVIER SCIENCE INC, 2021
- 2021
- English.
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In: Journal of Investigative Dermatology. - : ELSEVIER SCIENCE INC. - 0022-202X .- 1523-1747. ; 141:8, s. 2037-2048
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Abstract
Subject headings
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- Inflammatory diseases, including psoriasis, are characterized by changes in redox regulation. The MTH1 prevents the incorporation of oxidized nucleotides during DNA replication. Using MTH1 small-molecule inhibitors, we found induced apoptosis through 8-oxodeoxyguanosine triphosphate accumulation and DNA double-strand breaks after oxidative stress in normal and malignant keratinocytes. In psoriasis, we detected increased MTH1 expression in lesional skin and PBMCs compared with that in the controls. Using the imiquimod psoriasis mouse model, we found that MTH1 inhibition diminished psoriatic histological characteristics and normalized the levels of neutrophils and T cells in the skin and skin-draining lymph nodes. The inhibition abolished the expression of T helper type 17-associated cytokines in the skin, which was in line with decreased levels of IL-17-producing gd T cells in lymph nodes. In human keratinocytes, MTH1 inhibition prevented the upregulation of IL-17-downstream genes, which was independent of ROS-induced apoptosis. In conclusion, our data support MTH1 inhibition using small molecules suitable for topical application as a promising therapeutic approach to psoriasis.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Bivik Eding, Cec ...
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Köhler, Ines
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Verma, Deepti
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Sjögren, Florenc ...
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Bamberg, Claudia
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Karsten, Stella
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show more...
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Pham, Therese
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Scobie, Martin
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Helleday, Thomas
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Berglund, Ulrika ...
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Enerbäck, Charlo ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Journal of Inves ...
- By the university
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Linköping University
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Karolinska Institutet