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  1. 30 大学院医学系研究科・医学部
  2. 30D 学位論文
  3. 博士論文 本文
  4. 2023年度

MicroRNA Profiles in Intestinal Epithelial Cells in a Mouse Model of Sepsis

http://hdl.handle.net/10076/0002000767
http://hdl.handle.net/10076/0002000767
0892c22b-2e1d-456b-8881-77ba5702bf47
名前 / ファイル ライセンス アクション
2023DM0316.pdf 2023DM0316.pdf (1.3 MB)
Item type 学位論文 / Thesis or Dissertation(1)
公開日 2024-05-13
タイトル
タイトル MicroRNA Profiles in Intestinal Epithelial Cells in a Mouse Model of Sepsis
言語 en
言語
言語 eng
キーワード
言語 en
主題Scheme Other
主題 sepsis
キーワード
言語 en
主題Scheme Other
主題 cecal slurry injection
キーワード
言語 en
主題Scheme Other
主題 inflammation
キーワード
言語 en
主題Scheme Other
主題 intestinal epithelial cell
キーワード
言語 en
主題Scheme Other
主題 miRNA
資源タイプ
資源タイプ識別子 http://purl.org/coar/resource_type/c_db06
資源タイプ doctoral thesis
アクセス権
アクセス権 open access
アクセス権URI http://purl.org/coar/access_right/c_abf2
著者 CAIDENGBATE, SIQINGAOWA

× CAIDENGBATE, SIQINGAOWA

en CAIDENGBATE, SIQINGAOWA

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抄録
内容記述タイプ Abstract
内容記述 Abstract: Sepsis is a systemic inflammatory disorder that leads to the dysfunction of multiple organs. In the intestine, the deregulation of the epithelial barrier contributes to the development of sepsis by triggering continuous exposure to harmful factors. However, sepsis induced epigenetic changes in gene-regulation networks within intestinal epithelial cells (IECs) remain unexplored. In this study, we analyzed the expression profile of microRNAs (miRNAs) in IECs isolated from a mouse model of sepsis generated via cecal slurry injection. Among 239 miRNAs, 14 miRNAs were upregulated, and 9 miRNAs were downregulated in the IECs by sepsis. Upregulated miRNAs in IECs from septic mice, particularly miR-149-5p, miR-466q, miR-495, and miR-511-3p, were seen to exhibit complex and global effects on gene regulation networks. Interestingly, miR-511-3p has emerged as a diagnostic marker in this sepsis model due to its increase in blood in addition to IECs. As expected, mRNAs in the IECs were remarkably altered by sepsis; specifically, 2248 mRNAs were decreased, while 612 mRNAs were increased. This quantitative bias may be possibly derived, at least partly, from the direct effects of the sepsis-increased miRNAs on the comprehensive expression of mRNAs. Thus, current in silico data indicate that there are dynamic regulatory responses of miRNAs to sepsis in IECs. In addition, the miRNAs that were increased with sepsis had enriched downstream pathways including Wnt signaling, which is associated with wound healing, and FGF/FGFR signaling, which has been linked to chronic inflammation and fibrosis. These modifications in miRNA networks in IECs may lead to both pro- and anti-inflammatory effects in sepsis. The four miRNAs discovered above were shown to putatively target LOX, PTCH1, COL22A1, FOXO1, or HMGA2, via in silico analysis, which were associated with Wnt or inflammatory pathways and selected for further study. The expressions of these target genes were downregulated in sepsis IECs, possibly through posttranscriptional modifications of these miRNAs. Taken together, our study suggests that IECs display a distinctive miRNA profile which is capable of comprehensively and functionally reshaping the IEC-specific mRNA landscape in a sepsis model.
言語 en
内容記述
内容記述タイプ Other
内容記述 本文/Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan
内容記述
内容記述タイプ Other
内容記述 17p
書誌情報
発行日 2024-03-25
DOI
識別子タイプ DOI
関連識別子 10.3390/cells12050726
フォーマット
内容記述タイプ Other
内容記述 application/pdf
出版者
出版者 三重大学
出版者(ヨミ)
値 ミエダイガク
学位名
学位名 博士(医学)
学位授与機関
学位授与機関識別子Scheme kakenhi
学位授与機関識別子 14101
学位授与機関名 三重大学
学位授与年月日
学位授与年月日 2024-03-25
学位授与番号
学位授与番号 甲医学第2240号
ノート
資源タイプ(三重大)
値 Doctoral Dissertation / 博士論文
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