Selenium and the 15kDa Selenoprotein Impact Colorectal Tumorigenesis by Modulating Intestinal Barrier Integrity.

Selenium and the 15kDa Selenoprotein Impact Colorectal Tumorigenesis by Modulating Intestinal Barrier Integrity.
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DOI:
10.3390/ijms221910651
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发表时间:
2021-09-30
影响因子:
5.6
通讯作者:
Tsuji PA
Tsuji PA
中科院分区:
生物学2区
文献类型:
--
作者:
Canter JA;Ernst SE;Peters KM;Carlson BA;Thielman NRJ;Grysczyk L;Udofe P;Yu Y;Cao L;Davis CD;Gladyshev VN;Hatfield DL;Tsuji PA

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硒蛋白在哺乳动物的许多细胞功能和生化途径中发挥重要作用。我们以前的研究表明,15 kDa硒蛋白(Selenof)的缺陷显着减少异常隐窝灶(ACF)的形成在氧化偶氮甲烷(AOM)诱导的结肠癌小鼠模型。本研究的目的是研究硒对炎症性肿瘤发生的影响,以及膳食硒是否改变了这些影响。在断奶后的20周内,Selenof敲除(KO)小鼠和同窝对照小鼠喂食亚硒酸钠不足、充足或高的饮食。用AOM和葡聚糖硫酸钠诱导结肠肿瘤。令人惊讶的是,KO小鼠的ACF显著减少,但肿瘤数量与同窝对照小鼠相似。除了通过组织组织学的结构差异外,还评估了炎性结直肠癌中重要基因和上皮屏障功能相关基因的表达。我们的研究结果指出,Selenof在肠屏障完整性和粘膜和粘膜下层中腺和产生粘蛋白的杯状细胞的结构变化中的潜在作用,这可能决定肿瘤发展的类型。
Selenoproteins play important roles in many cellular functions and biochemical pathways in mammals. Our previous study showed that the deficiency of the 15 kDa selenoprotein (Selenof) significantly reduced the formation of aberrant crypt foci (ACF) in a mouse model of azoxymethane (AOM)-induced colon carcinogenesis. The objective of this study was to examine the effects of Selenof on inflammatory tumorigenesis, and whether dietary selenium modified these effects. For 20 weeks post-weaning, Selenof-knockout (KO) mice and littermate controls were fed diets that were either deficient, adequate or high in sodium selenite. Colon tumors were induced with AOM and dextran sulfate sodium. Surprisingly, KO mice had drastically fewer ACF but developed a similar number of tumors as their littermate controls. Expression of genes important in inflammatory colorectal cancer and those relevant to epithelial barrier function was assessed, in addition to structural differences via tissue histology. Our findings point to Selenof’s potential role in intestinal barrier integrity and structural changes in glandular and mucin-producing goblet cells in the mucosa and submucosa, which may determine the type of tumor developing.
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