Propionate Enhances Cell Speed and Persistence to Promote Intestinal Epithelial Turnover and Repair.
Propionate Enhances Cell Speed and Persistence to Promote Intestinal Epithelial Turnover and Repair.
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DOI：
10.1016/j.jcmgh.2020.11.011
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发表时间：
2021
影响因子：
7.2
通讯作者：
Cong Y
中科院分区：
文献类型：
--
作者：
Bilotta AJ;Ma C;Yang W;Yu Y;Yu Y;Zhao X;Zhou Z;Yao S;Dann SM;Cong Y
肠道细菌来源的短链脂肪酸（SCFAs）在维持肠道内稳态中起着至关重要的作用。然而，SCFAs如何调节上皮更新和组织修复仍然不完全清楚。在这项研究中，我们研究了SCFA丙酸盐如何调节细胞迁移，以促进上皮更新和修复。使用小鼠小肠上皮细胞（MSIE）和人Caco-2细胞来确定SCFAs对体外基因表达、增殖、迁移和细胞铺展的影响。使用视频显微镜和单细胞跟踪来评估细胞迁移动力学。使用5-溴-2 '-脱氧尿苷（BrdU）和羟基脲来评估SCFA对体内迁移的影响。最后，使用葡聚糖硫酸钠（DSS）的急性结肠炎模型来检查SCFA在体内的作用。使用视频显微镜和单细胞跟踪，我们发现丙酸盐通过增强细胞铺展和极化促进肠上皮细胞迁移，从而导致细胞速度和持久性增加。丙酸的这种新功能依赖于抑制I类组蛋白脱乙酰酶（HDAC）和GPR 43，并需要信号转导和转录激活因子3（STAT 3）。此外，在体内使用5-溴-2 '-脱氧尿苷（BrdU）和羟基脲，我们发现丙酸盐在稳态条件下增强了细胞向隐窝-绒毛轴的迁移，同时还保护了实验性结肠炎中的溃疡形成。我们的研究结果表明，丙酸刺激细胞迁移的HDAC抑制，GPR 43和STAT 3依赖的方式的机制，并建议丙酸起着重要的作用，上皮细胞迁移独立的增殖。
Gut bacteria-derived short-chain fatty acids (SCFAs) play crucial roles in the maintenance of intestinal homeostasis. However, how SCFAs regulate epithelial turnover and tissue repair remain incompletely understood. In this study, we investigated how the SCFA propionate regulates cell migration to promote epithelial renewal and repair. Mouse small intestinal epithelial cells (MSIE) and human Caco-2 cells were used to determine the effects of SCFAs on gene expression, proliferation, migration, and cell spreading in vitro. Video microscopy and single cell tracking were used to assess cell migration kinetically. 5-bromo-2’-deoxyuridine (BrdU) and hydroxyurea were used to assess the effects of SCFAs on migration in vivo. Lastly, an acute colitis model using dextran sulfate sodium (DSS) was used to examine the effects of SCFAs in vivo. Using video microscopy and single cell tracking, we found that propionate promoted intestinal epithelial cell migration by enhancing cell spreading and polarization, which led to increases in both cell speed and persistence. This novel function of propionate was dependent on inhibition of class I histone deacetylases (HDAC) and GPR43 and required signal transducer and activator of transcription 3 (STAT3). Furthermore, using 5-bromo-2’-deoxyuridine (BrdU) and hydroxyurea in vivo, we found that propionate enhanced cell migration up the crypt-villus axis under homeostatic conditions, while also protecting against ulcer formation in experimental colitis. Our results demonstrate a mechanism by which propionate stimulates cell migration in an HDAC inhibition, GPR43, and STAT3 dependent manner, and suggest that propionate plays an important role in epithelial migration independent of proliferation.
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影响因子：
4.2
作者：
Chen, Haijun;Yang, Zhengduo;Ding, Chunyong;Chu, Lili;Zhang, Yusong;Terry, Kristin;Liu, Huiling;Shen, Qiang;Zhou, Jia
通讯作者：
Zhou, Jia
Warburg效应决定了丁酸酯介导的组蛋白乙酰化和细胞增殖的机制。
影响因子：
16
作者：
Donohoe, Dallas R.;Collins, Leonard B.;Wali, Aminah;Bigler, Rebecca;Sun, Wei;Bultman, Scott J.
通讯作者：
Bultman, Scott J.
影响因子：
29
作者：
Donohoe DR;Garge N;Zhang X;Sun W;O'Connell TM;Bunger MK;Bultman SJ
通讯作者：
Bultman SJ
影响因子：
24.5
作者：
FINNIE, IA;DWARAKANATH, AD;RHODES, JM
通讯作者：
RHODES, JM
影响因子：
29.4
作者：
Ben, Qiwen;Sun, Yunwei;Yuan, Yaozong
通讯作者：
Yuan, Yaozong