Lineage-specific expression of bestrophin-2 and bestrophin-4 in human intestinal epithelial cells.
Lineage-specific expression of bestrophin-2 and bestrophin-4 in human intestinal epithelial cells.
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DOI：
10.1371/journal.pone.0079693
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Watanabe M
中科院分区：
文献类型：
--
作者：
Ito G;Okamoto R;Murano T;Shimizu H;Fujii S;Nakata T;Mizutani T;Yui S;Akiyama-Morio J;Nemoto Y;Okada E;Araki A;Ohtsuka K;Tsuchiya K;Nakamura T;Watanabe M
肠上皮细胞（IECs）调节阴离子的吸收和分泌，如HCO3-或Cl-。Bestrophin基因是一组新发现的钙活化Cl-通道（CaCCs）。研究表明，在人类四种bestrophin家族基因中，bestrophin-2 （BEST2）和bestrophin-4 （BEST4）可能在肠组织内表达。与此一致的是，一项研究表明，人类结肠杯状细胞表达了BEST2。然而，它们沿着胃肠道的精确表达模式，或者表达这些基因的细胞的谱系特异性，在很大程度上仍然未知。在这里，我们证明了BEST2和BEST4在人iec中以不同的、谱系特异性的方式在体内表达。BEST2仅在结肠杯状细胞中表达，而BEST4在小肠和结肠的吸收细胞中均有表达。此外，我们发现，在溃疡性结肠炎的活动性病变中，由于杯状细胞被耗尽，BEST2的表达显著下调，这表明在正常和病理条件下，BEST2的表达仅限于杯状细胞。同样，Notch抑制剂LY411575诱导杯状细胞分化，在muc2阳性HT-29细胞中，显著上调的不是BEST4，而是BEST2的表达。相反，诱导吸收性细胞分化上调绒毛蛋白阳性Caco-2细胞中BEST4的表达。此外，我们发现Notch活性的上调或下调会导致在LS174T细胞中分别优先表达BEST4或BEST2。这些结果共同证实了BEST2和BEST4可以被添加到人类IECs的谱系特异性基因中，因为它们能够分别清楚地识别结肠起源的杯状细胞和一个独特的吸收细胞亚群。
Intestinal epithelial cells (IECs) regulate the absorption and secretion of anions, such as HCO3- or Cl-. Bestrophin genes represent a newly identified group of calcium-activated Cl- channels (CaCCs). Studies have suggested that, among the four human bestrophin-family genes, bestrophin-2 (BEST2) and bestrophin-4 (BEST4) might be expressed within the intestinal tissue. Consistently, a study showed that BEST2 is expressed by human colonic goblet cells. However, their precise expression pattern along the gastrointestinal tract, or the lineage specificity of the cells expressing these genes, remains largely unknown. Here, we show that BEST2 and BEST4 are expressed in vivo, each in a distinct, lineage-specific manner, in human IECs. While BEST2 was expressed exclusively in colonic goblet cells, BEST4 was expressed in the absorptive cells of both the small intestine and the colon. In addition, we found that BEST2 expression is significantly down-regulated in the active lesions of ulcerative colitis, where goblet cells were depleted, suggesting that BEST2 expression is restricted to goblet cells under both normal and pathologic conditions. Consistently, the induction of goblet cell differentiation by a Notch inhibitor, LY411575, significantly up-regulated the expression of not BEST4 but BEST2 in MUC2-positive HT-29 cells. Conversely, the induction of absorptive cell differentiation up-regulated the expression of BEST4 in villin-positive Caco-2 cells. In addition, we found that the up- or down-regulation of Notch activity leads to the preferential expression of either BEST4 or BEST2, respectively, in LS174T cells. These results collectively confirmed that BEST2 and BEST4 could be added to the lineage-specific genes of humans IECs due to their abilities to clearly identify goblet cells of colonic origin and a distinct subset of absorptive cells, respectively.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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DOI：
10.1006/bbrc.1999.0168
发表时间：
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影响因子：
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DOI：
10.1152/ajpgi.00015.2002
发表时间：
2002-07-01
影响因子：
4.5
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Haskó, G