Fusobacterium nucleatum Promotes the Development of Ulcerative Colitis by Inducing the Autophagic Cell Death of Intestinal Epithelial.
Fusobacterium nucleatum Promotes the Development of Ulcerative Colitis by Inducing the Autophagic Cell Death of Intestinal Epithelial.
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DOI：
10.3389/fcimb.2020.594806
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发表时间：
2020
影响因子：
5.7
通讯作者：
Dong W
中科院分区：
文献类型：
--
作者：
Su W;Chen Y;Cao P;Chen Y;Guo Y;Wang S;Dong W
越来越多的证据表明，肠道微生物群，特别是具核梭杆菌（F。核质）与肠免疫疾病如溃疡性结肠炎（UC）相关。F.核质促进肠上皮细胞（IEC）死亡的作用尚不清楚。在此，我们研究了F。nucleatum可导致UC中IEC死亡。我们首先检测了F的丰度。分析UC组织中核仁的表达与UC临床特征的关系。接下来，我们探讨了F.核质促进肠上皮细胞死亡在体外和体内。此外，我们还提取了F. nucleatum，并检测了F. nucleatum通过LPS加重UC。结果表明，F. UC组织中有大量的核质，并与临床特征相关。此外，我们还证明了F.核仁及其LPS通过促进IEC自噬而加重IEC死亡。此外，自噬抑制剂氯喹（CQ）、3-甲基腺嘌呤（3-MA）或Atg 5沉默可阻止由F. nucleatum，提示F.有核质可能通过激活自噬性细胞死亡而导致UC。所有的结果揭示了F.因此，通过抑制过度的IEC自噬和自噬性细胞死亡，为UC的治疗提供了新的视角。
There is a growing body of evidence which suggests that intestinal microbiota, especially Fusobacterium nucleatum (F. nucleatum), are associated with intestinal immune disease such as ulcerative colitis (UC). The mechanism by which F. nucleatum promotes intestinal epithelial cell (IEC) death remained undefined. Here, we investigated the potential mechanisms about how F. nucleatum aggravates IEC death in UC. We first detected the abundance of F. nucleatum in UC tissues and analyzed its relationship with the clinical characteristics of UC. Next, we explored whether F. nucleatum promotes intestinal epithelial cell death in vitro and in vivo. Furthermore, we extracted lipopolysaccharide (LPS) of the F. nucleatum and examined whether F. nucleatum exacerbates UC via LPS. Our results indicated that F. nucleatum was abundant in UC tissues and was correlated with clinical characteristics. In addition, we demonstrated that F. nucleatum and its LPS aggravated IEC death by promoted IEC autophagy. Furthermore, autophagy inhibitors, chloroquine (CQ), 3-methyladenine (3-MA) or Atg5 silencing prevented IEC death mediated by F. nucleatum, which suggests F. nucleatum may contribute to UC by activating autophagic cell death. All our results uncover a vital role of F. nucleatum in autophagic cell death and UC, giving rise to a new sight for UC therapy by inhibiting excessive IEC autophagy and autophagic cell death.
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影响因子：
4.7
作者：
Byun, Joo-Yun;Yoon, Chang-Hwan;Lee, Su-Jae
通讯作者：
Lee, Su-Jae
影响因子：
--
作者：
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Li JM
影响因子：
3.1
作者：
Dharmani, Poonam;Strauss, Jaclyn;Chadee, Kris
通讯作者：
Chadee, Kris
影响因子：
3.1
作者：
Kaplan, Christopher W.;Ma, Xiaoyuan;Shi, Wenyuan
通讯作者：
Shi, Wenyuan
淫羊藿苷及磷酸化淫羊藿苷对LPS诱导的肠上皮细胞损伤的保护作用
影响因子：
7.5
作者：
Xiong, Wen;Ma, Haoyue;Wang, Zili
通讯作者：
Wang, Zili