Peptidylarginine deiminase 2 (PAD2) contributes the pathogenesis of TNBS-induced murine colitis in relation to extracellular trap formation
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- Yasuda Hiroyuki
- Dept. Pharmacol. Exp. Ther., Kyoto Pharm. Univ.
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- Shimomura Marino
- Dept. Pharmacol. Exp. Ther., Kyoto Pharm. Univ.
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- Uno Ayaka
- Dept. Pharmacol. Exp. Ther., Kyoto Pharm. Univ.
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- Koda Saya
- Dept. Pharmacol. Exp. Ther., Kyoto Pharm. Univ.
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- Tanaka Yoshiya
- Dept. Pharmacol. Exp. Ther., Kyoto Pharm. Univ.
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- Saito Michiko
- Bio-Sci. Res. Ctr., Kyoto Pharm. Univ.
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- Matsumoto Kenjiro
- Dept. Pharmacol. Exp. Ther., Kyoto Pharm. Univ.
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- Kato Shinichi
- Dept. Pharmacol. Exp. Ther., Kyoto Pharm. Univ.
Bibliographic Information
- Other Title
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- PAD2のTNBS誘導性大腸炎の病態における役割:細胞外トラップ誘導との関連
Abstract
<p>Peptidylarginine deiminase 2 (PAD2), an enzyme that converts peptidyl-arginine to peptidyl-citrulline, is widely distributed in various tissues and cells. Although PAD4 is known to be involved in various inflammatory and immune diseases via neutrophil extracellular trap (NETosis) formation, the pathophysiological roles of PAD2 have not been fully understood. The present study investigated the pathogenic role of PAD2 in inflammatory bowel disease using trinitrobenzene sulfonic acid (TNBS)-induced murine colitis model. PAD2-deficent (PAD2KO) mice were generated by CRISPR-Cas9-mediated genomic editing. Colitis was induced in PAD2KO and its wild-type (WT) mice by intrarectal injection of TNBS. The extracellular trap formation was detected by triple immunohistochemical staining with myeloperoxidase (MPO), citrullinated histone H3, and DNA (Sytox Blue). TNBS injection induced body weight loss, extensive colonic erosions, and ulceration accompanied by an increase in MPO activity in WT mice, but these responses were significantly attenuated in KO mice. Daily administration of Cl-amidine (an inhibitor of pan-PADs) or DNase Ⅰ (an inhibitor of extracellular trap formation) also significantly reduced the severity of TNBS-induced colitis. Furthermore, the extracellular trap formation was upregulated by TNBS injection at lesion sites, but this response was apparently attenuated by PAD2KO and Cl-amidine injection. These findings suggest that PAD2 contributes to the pathogenesis of TNBS-induced colitis probably via inhibition of extracellular traps.</p>
Journal
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- Proceedings for Annual Meeting of The Japanese Pharmacological Society
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Proceedings for Annual Meeting of The Japanese Pharmacological Society 95 (0), 2-P-151-, 2022
Japanese Pharmacological Society
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Keywords
Details 詳細情報について
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- CRID
- 1390854717648554880
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- ISSN
- 24354953
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- Text Lang
- ja
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- Data Source
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- JaLC
- Crossref
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- Abstract License Flag
- Disallowed