Schlafen-3: a novel regulator of intestinal differentiation.
Schlafen-3: a novel regulator of intestinal differentiation.
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DOI：
10.1016/j.bbrc.2009.08.094
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发表时间：
2009-10-30
影响因子：
3.1
通讯作者：
Majumdar, Adhip P. N.
中科院分区：
文献类型：
--
作者：
Patel, Vaishali B.;Yu, Yingjie;Das, Jayanta K.;Patel, Bhaumik B.;Majumdar, Adhip P. N.
Schlafen-3 （Slfn-3）是一个新的基因，已被证明是增殖的负调控因子。目前的研究是为了确定Slfn-3是否可能在调节细胞分化中发挥作用。丁酸是一种短链脂肪酸，在大鼠小肠IEC-6细胞中引起碱性磷酸酶（ALP）活性升高，从而诱导肠细胞分化，同时也使Slfn-3的表达显著增加。此外，Slfn-3的过表达引起IEC-6细胞ALP活性的刺激，丁酸盐加重了这种刺激。另一方面，Slfn-3 -si- rna对Slfn-3的下调大大减弱了丁酸盐介导的IEC-6细胞分化的诱导作用。此外，我们观察到结肠癌HCT-116细胞中Slfn-3的表达增加刺激TGF-β的表达并调节其下游效应物的表达，如p27kip1的表达增加和CDK-2的下调。此外，Slfn-3上调E-cadherin的表达，下调β-catenin的表达。综上所述，我们的数据表明，Slfn-3在调节肠黏膜分化中起着关键作用。此外，我们的数据还表明TGF-β信号通路在介导slfn-3诱导的分化中起重要作用。
Schlafen-3 (Slfn-3), a novel gene, has been shown to be a negative regulator of proliferation. The current investigation was undertaken to determine whether Slfn-3 might play a role in regulating cellular differentiation. Butyric acid, a short chain fatty acid, which induced differentiation of intestinal cells as evidenced by increased alkaline phosphatase (ALP) activity in the rat small intestinal IEC-6 cells, also produced a marked increase in Slfn-3 expression. Furthermore, overexpression of Slfn-3 caused stimulation of ALP activity in IEC-6 cells, which was exacerbated by butyrate. On the other hand, downregulation of Slfn-3 by slfn-3-si-RNA greatly attenuated the butyrate mediated induction of differentiation of IEC-6 cells. Additionally, we observed that increased expression of Slfn-3 in colon cancer HCT-116 cells stimulated TGF-β expression and modulated expression of its downstream effectors as evidenced by increased expression of p27kip1 and downregulation of CDK-2. In addition, Slfn-3 increases E-cadherin expression but downregulates β-catenin. In conclusion, our data show that Slfn-3 plays a critical role in regulating intestinal mucosal differentiation. Furthermore our data also show that TGF-β signaling pathway plays an important role in mediating slfn-3 induced differentiation.
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影响因子：
14.9
作者：
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通讯作者：
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DOI：
10.1083/jcb.200311021
发表时间：
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期刊：
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影响因子：
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