Scholarlink

<p>Peptidylarginine deiminase 2 (PAD2) is an enzyme that converts arginine to citrulline and is involved in diseases, such as Alzheimer’s diseases, fibrosis and cancer. However, its role in inflammatory bowel disease remains unclear. In this study, we investigated the pathogenic effects of PAD2 on inflammatory bowel disease using a trinitrobenzene sulfonic acid (TNBS)-induced murine colitis model. PAD2-deficient (PAD2KO) mice were generated using CRISPR/Cas9-mediated genomic editing. TNBS injection resulted in body weight loss, extensive colonic erosion, and ulceration in wild-type (WT) mice. However, these responses were significantly attenuated in PAD2KO mice. TNBS-induced increases in myeloperoxidase activity, inflammatory cytokine expression, and macrophage extracellular traps (METs) induction in the colon were significantly reduced in PAD2KO. Furthermore, METs were triggered in peritoneal macrophages obtained from WT mice by A23187 and phorbol myristate acetate, and notably, these responses were not abolished in PAD2KO mice. Moreover, inflammatory cytokine expression and M1 macrophage polarization in peritoneal macrophages obtained from PAD2KO mice was lower than that in peritoneal macrophages from WT mice. Overall, PAD2 contributes to the pathogenesis of TNBS-induced colitis by regulating inflammatory cytokine expression in macrophages through METs-independent pathways. Therefore, PAD2 is a promising target for treating inflammatory bowel disease.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Peptidylarginine deiminase 2 contributes to pathogenesis in trinitrobenzenesulfonic acid-induced colitis through macrophage extracellular trap-independent pathways

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月18日

查看全文
  • Hiroyuki Yasuda,
  • Michiko Saito,
  • Shusaku Hayashi,
  • Shinichi Kato

摘要

Peptidylarginine deiminase 2 (PAD2) is an enzyme that converts arginine to citrulline and is involved in diseases, such as Alzheimer’s diseases, fibrosis and cancer. However, its role in inflammatory bowel disease remains unclear. In this study, we investigated the pathogenic effects of PAD2 on inflammatory bowel disease using a trinitrobenzene sulfonic acid (TNBS)-induced murine colitis model. PAD2-deficient (PAD2KO) mice were generated using CRISPR/Cas9-mediated genomic editing. TNBS injection resulted in body weight loss, extensive colonic erosion, and ulceration in wild-type (WT) mice. However, these responses were significantly attenuated in PAD2KO mice. TNBS-induced increases in myeloperoxidase activity, inflammatory cytokine expression, and macrophage extracellular traps (METs) induction in the colon were significantly reduced in PAD2KO. Furthermore, METs were triggered in peritoneal macrophages obtained from WT mice by A23187 and phorbol myristate acetate, and notably, these responses were not abolished in PAD2KO mice. Moreover, inflammatory cytokine expression and M1 macrophage polarization in peritoneal macrophages obtained from PAD2KO mice was lower than that in peritoneal macrophages from WT mice. Overall, PAD2 contributes to the pathogenesis of TNBS-induced colitis by regulating inflammatory cytokine expression in macrophages through METs-independent pathways. Therefore, PAD2 is a promising target for treating inflammatory bowel disease.