α-Amylase expressed in human small intestinal epithelial cells is essential for cell proliferation and differentiation

α-Amylase expressed in human small intestinal epithelial cells is essential for cell proliferation and differentiation
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DOI:
10.1002/jcb.29357
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发表时间:
2019-09-03
影响因子:
4
通讯作者:
Ogawa, Haruko
Ogawa, Haruko
中科院分区:
生物学2区
文献类型:
--
作者:
Date, Kimie;Yamazaki, Tomomi;Ogawa, Haruko

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在淀粉降解中起重要作用的α-淀粉酶主要在胰腺和唾液腺中表达。人类α-淀粉酶也在其他组织中检测到,但尚不清楚α-淀粉酶是在每个组织中内源性表达,还是与胰腺或唾液腺表达的外源性淀粉酶混合表达。此外,在胰腺和唾液腺以外的组织中检测到的这些α-淀粉酶的生物学意义尚未阐明。我们发现人的α-淀粉酶在肠上皮细胞中表达,并分析了抑制α-淀粉酶表达的效果。α-淀粉酶在人类正常组织中的表达水平仅次于胰腺,在十二指肠中的信使RNA水平第二高。Caco-2肠上皮细胞提取液中可检测到α-淀粉酶,但不能分泌到培养液中。α-淀粉酶的表达量随培养时间的延长而增加,表明α-淀粉酶在小肠上皮细胞中表达,而不是在结肠上皮细胞中表达,这是因为细胞在达到培养汇合时会自发分化,表现出小肠上皮细胞的特征,而不是结肠细胞。在Caco-2细胞中表达的α-淀粉酶具有酶活性,经鉴定为AMY2B,是胰腺α-淀粉酶的两种亚型之一。小干扰RNA抑制α-淀粉酶表达,抑制细胞分化和增殖。这些结果首次证明了α-淀粉酶在人类肠道上皮细胞中表达,并影响细胞的增殖和分化。这种α-淀粉酶可能会诱导小肠上皮细胞的增殖和分化,支持细胞的快速周转,以维持健康的肠腔。
alpha-Amylase, which plays an essential role in starch degradation, is expressed mainly in the pancreas and salivary glands. Human alpha-amylase is also detected in other tissues, but it is unclear whether the alpha-amylase is endogenously expressed in each tissue or mixed exogenously with one expressed by the pancreas or salivary glands. Furthermore, the biological significance of these alpha-amylases detected in tissues other than the pancreas and salivary glands has not been elucidated. We discovered that human alpha-amylase is expressed in intestinal epithelial cells and analyzed the effects of suppressing alpha-amylase expression. alpha-Amylase was found to be expressed at the second-highest messenger RNA level in the duodenum in human normal tissues after the pancreas. alpha-Amylase was detected in the cell extract of Caco-2 intestinal epithelial cells but not secreted into the culture medium. The amount of alpha-amylase expressed increased depending on the length of the culture of Caco-2 cells, suggesting that alpha-amylase is expressed in small intestine epithelial cells rather than the colon because the cells differentiate spontaneously upon reaching confluence in culture to exhibit the characteristics of small intestinal epithelial cells rather than colon cells. The alpha-amylase expressed in Caco-2 cells had enzymatic activity and was identified as AMY2B, one of the two isoforms of pancreatic alpha-amylase. The suppression of alpha-amylase expression by small interfering RNA inhibited cell differentiation and proliferation. These results demonstrate for the first time that alpha-amylase is expressed in human intestinal epithelial cells and affects cell proliferation and differentiation. This alpha-amylase may induce the proliferation and differentiation of small intestine epithelial cells, supporting a rapid turnover of cells to maintain a healthy intestinal lumen.