A further study on a disturbance of intestinal epithelial cell population and kinetics in APC1638T mice

A further study on a disturbance of intestinal epithelial cell population and kinetics in APC1638T mice
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APC1638T小鼠肠上皮细胞群和动力学紊乱的进一步研究

DOI:
10.1007/s00795-020-00279-x
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发表时间:
2021
影响因子:
1.8
通讯作者:
Takao Senda
Takao Senda
中科院分区:
医学4区
文献类型:
--
作者:
Wenduerma;Nami O. Yamada;Tuya Wang;Takao Senda

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大肠腺瘤性息肉病(Adenomatous polyposis coli,APC)是一种已知的抑癌基因,通过其多个结合域发挥多种功能。我们继续研究APC 1638 T/1638 T小鼠(APC 1638 T小鼠),以阐明APC除抑瘤外的功能。APC 1638 T小鼠的一个显著特征是它们没有肿瘤并且与APC +/+小鼠(WT小鼠)一样长。在此之前,我们发现APC 1638 T小鼠空肠中的隐窝-绒毛轴的长度与WT小鼠相比显著延长。APC 1638 T小鼠的杯状细胞、潘氏细胞和肠内分泌细胞群也发生了紊乱。在此,我们进一步分析了APC 1638 T小鼠的肠道稳态失调,重点是肠道干细胞(ISC)谱系的增殖和分化,以及绒毛尖端的凋亡细胞脱落。我们发现,ISC谱系的增殖是正常控制的,然而,凋亡细胞的脱落过程中显着延迟APC 1638 T小鼠空肠。此外,在APC 1638 T小鼠空肠中微折叠细胞(M细胞)的数量显著增加。提示APC 1638 T小鼠小肠ISCs的分化过程和肠上皮细胞的更新过程均受到干扰,导致了APC 1638 T小鼠空肠绒毛的伸长。
Adenomatous polyposis coli (APC), a well-known anti-oncogene, is considered to have multiple functions through its several binding domains. We have continuingly studiedAPC1638T/1638Tmice (APC1638T mice) to elucidate the functions of APC other than tumor suppression. A distinctive feature of the APC1638T mice is they are tumor free and live as long asAPC+/+mice (WT mice). Previously, we found the length of crypt–villus axis in the jejunum was significantly elongated in APC1638T mice compared with that of WT mice. The populations of goblet cells, Paneth cells, and enteroendocrine cells were also disordered in APC1638T mice. Here, we further analyzed the intestinal dyshomeostasis in APC1638T mice, focusing on the proliferation and differentiation of intestinal stem cell (ISC) lineages, and apoptotic cell shedding at the villus tips. We found that the proliferation of ISC lineages was normally controlled; however, the shedding process of apoptosis cells was significantly delayed in the APC1638T mouse jejunum. Furthermore, the number of microfold cells (M cells) was significantly increased in the APC1638T mouse jejunum. Our data suggested both differentiation process of ISCs and turnover process of intestinal epithelia were disturbed in APC1638T mice, and that contributed to the villus elongation in the APC1638T mouse jejunum.
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发表时间: 2012-09-01
影响因子: 5.3
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DOI: --
发表时间: 1995
期刊: Oncogene
影响因子: 8
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