Loss of Sirt1 function improves intestinal anti-bacterial defense and protects from colitis-induced colorectal cancer.

Loss of Sirt1 function improves intestinal anti-bacterial defense and protects from colitis-induced colorectal cancer.
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SIRT1功能的丧失可改善肠道抗细菌防御,并保护结肠炎诱发的大肠癌。

DOI:
10.1371/journal.pone.0102495
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Auwerx J
Auwerx J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Lo Sasso G;Ryu D;Mouchiroud L;Fernando SC;Anderson CL;Katsyuba E;Piersigilli A;Hottiger MO;Schoonjans K;Auwerx J

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肠道中潘氏细胞和杯状细胞的功能障碍导致炎症性肠病(IBD)和结肠炎相关性结直肠癌(CAC)。在这里,我们报告了依赖NAD+的组蛋白去乙酰基酶SIRT1在控制抗菌防御中的作用。患有肠道特异性Sirt1缺陷(Sirt1int−/−)的小鼠有更多的潘氏细胞和杯状细胞,从而导致肠道微生物区系的重新排列。从机制上看,对小鼠肠道细胞成熟的影响是通过依赖于SIRT1的SPDEF乙酰化状态的变化来实现的,SPDEF是Paneth和杯状细胞的主要调节因子。我们的结果表明,靶向SIRT1可能对IBD和CAC的治疗有意义。
Dysfunction of Paneth and goblet cells in the intestine contributes to inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CAC). Here, we report a role for the NAD+-dependent histone deacetylase SIRT1 in the control of anti-bacterial defense. Mice with an intestinal specific Sirt1 deficiency (Sirt1int−/−) have more Paneth and goblet cells with a consequent rearrangement of the gut microbiota. From a mechanistic point of view, the effects on mouse intestinal cell maturation are mediated by SIRT1-dependent changes in the acetylation status of SPDEF, a master regulator of Paneth and goblet cells. Our results suggest that targeting SIRT1 may be of interest in the management of IBD and CAC.
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发表时间: 2013-08-06
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