論文

査読有り 国際誌
2018年10月23日

Regnase-1 controls colon epithelial regeneration via regulation of mTOR and purine metabolism.

Proceedings of the National Academy of Sciences of the United States of America
  • Yasuharu Nagahama
  • ,
  • Mayuko Shimoda
  • ,
  • Guoliang Mao
  • ,
  • Shailendra Kumar Singh
  • ,
  • Yuuki Kozakai
  • ,
  • Xin Sun
  • ,
  • Daisuke Motooka
  • ,
  • Shota Nakamura
  • ,
  • Hiroki Tanaka
  • ,
  • Takashi Satoh
  • ,
  • Kazuhiko Maeda
  • ,
  • Shizuo Akira

115
43
開始ページ
11036
終了ページ
11041
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1073/pnas.1809575115

Damage to intestinal epithelial cell (IEC) layers during intestinal inflammation is associated with inflammatory bowel disease. Here we show that the endoribonuclease Regnase-1 controls colon epithelial regeneration by regulating protein kinase mTOR (the mechanistic target of rapamycin kinase) and purine metabolism. During dextran sulfate sodium-induced intestinal epithelial injury and acute colitis, Regnase-1∆IEC mice, which lack Regnase-1 specifically in the intestinal epithelium, were resistant to body weight loss, maintained an intact intestinal barrier, and showed increased cell proliferation and decreased epithelial apoptosis. Chronic colitis and tumor progression were also attenuated in Regnase-1∆IEC mice. Regnase-1 predominantly regulates mTORC1 signaling. Metabolic analysis revealed that Regnase-1 participates in purine metabolism and energy metabolism during inflammation. Furthermore, increased expression of ectonucleotidases contributed to the resolution of acute inflammation in Regnase-1∆IEC mice. These findings provide evidence that Regnase-1 deficiency has beneficial effects on the prevention and/or blocking of intestinal inflammatory disorders.

リンク情報
DOI
https://doi.org/10.1073/pnas.1809575115
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30297433
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6205455
ID情報
  • DOI : 10.1073/pnas.1809575115
  • PubMed ID : 30297433
  • PubMed Central 記事ID : PMC6205455

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