Regulation of epithelial differentiation in rat intestine by intraluminal delivery of an adenoviral vector or silencing RNA coding for Schlafen 3.
Regulation of epithelial differentiation in rat intestine by intraluminal delivery of an adenoviral vector or silencing RNA coding for Schlafen 3.
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通过对腺病毒载体的腔内递送或沉默的schlafen 3编码RNA 3。
DOI：
10.1371/journal.pone.0079745
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Basson MD
中科院分区：
文献类型：
--
作者：
Kovalenko PL;Yuan L;Sun K;Kunovska L;Seregin S;Amalfitano A;Basson MD
虽然我们通过刺激肠细胞增殖来改善短肠综合征或粘膜萎缩，但针对肠细胞分化的研究较少。Schlafen 3 （Slfn3）是在IEC-6肠细胞分化过程中诱导的一种鲜为人知的蛋白。我们假设外源操纵Slfn3可以调节体内肠细胞分化。将编码Slfn3 cDNA的腺病毒载体（Ad-GFP-Slfn3）或Slfn3沉默RNA （siSlfn3）注入大鼠肠内。我们通过qRT-PCR、Western blot和免疫组织化学检测了Slfn3、绒毛蛋白、蔗糖-异麦芽糖酶（SI）、Dpp4和Glut2。我们还研究了Slfn3及其分化标志物在萎缩性失功能空肠黏膜和正常空肠隐绒毛轴中的表达。Ad-GFP-Slfn3增加了人Caco-2肠上皮细胞中Slfn3、villin和Dpp4的表达，而Ad-GFP不增加。体内空肠注射Ad-GFP-Slfn3与腹腔注射Ad-GFP相比，3天后黏膜Slfn3 mRNA升高。Slfn3过表达与所有四种分化标志物的增加有关。在体内将siSlfn3注射到大鼠空肠后3天，Slfn3和所有四种肠黏膜分化标志物以及Dpp4特异性活性均显著降低。内源性Slfn3在Roux-en-Y盲端吻合的萎缩黏膜中表达减少，分化标志物与AKT和p38信号同时表达。Slfn3在绒毛中的表达高于隐窝，与Glut2、SI和Dpp4平行。Slfn3是大鼠肠细胞分化的关键细胞内调节因子。了解Slfn3的作用机制可以在体内发现促进肠细胞分化和维持粘膜功能的靶点，促进肠内营养，提高黏膜萎缩或短肠综合征患者的生存率。
Although we stimulate enterocytic proliferation to ameliorate short gut syndrome or mucosal atrophy, less effort has been directed at enterocytic differentiation. Schlafen 3 (Slfn3) is a poorly understood protein induced during IEC-6 enterocytic differentiation. We hypothesized that exogenous manipulation of Slfn3 would regulate enterocytic differentiation in vivo. Adenoviral vector coding for Slfn3 cDNA (Ad-GFP-Slfn3) or silencing RNA for Slfn3 (siSlfn3) was introduced intraluminally into rat intestine. We assessed Slfn3, villin, sucrase-isomaltase (SI), Dpp4, and Glut2 by qRT-PCR, Western blot, and immunohistochemistry. We also studied Slfn3 and these differentiation markers in atrophic defunctionalized jejunal mucosa and the crypt-villus axis of normal jejunum. Ad-GFP-Slfn3 but not Ad-GFP increased Slfn3, villin and Dpp4 expression in human Caco-2 intestinal epithelial cells. Injecting Ad-GFP-Slfn3 into rat jejunum in vivo increased mucosal Slfn3 mRNA three days later vs. intraluminal Ad-GFP. This Slfn3 overexpression was associated with increases in all four differentiation markers. Injecting siSlfn3 into rat jejunum in vivo substantially reduced Slfn3 and all four intestinal mucosal differentiation markers three days later, as well as Dpp4 specific activity. Endogenous Slfn3 was reduced in atrophic mucosa from a blind-end Roux-en-Y anastomosis in parallel with differentiation marker expression together with AKT and p38 signaling. Slfn3 was more highly expressed in the villi than the crypts, paralleling Glut2, SI and Dpp4. Slfn3 is a key intracellular regulator of rat enterocytic differentiation. Understanding how Slfn3 works may identify targets to promote enterocytic differentiation and maintain mucosal function in vivo, facilitating enteral nutrition and improving survival in patients with mucosal atrophy or short gut syndrome.
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影响因子：
4.4
作者：
Kovalenko, Pavlo L.;Zhang, Zhentao;Fleet, James C.
通讯作者：
Fleet, James C.
影响因子：
5.6
作者：
Hahn, Hejin P.;Blount, Patricia L.;Odze, Robert D.
通讯作者：
Odze, Robert D.
DOI：
10.1152/ajpgi.90648.2008
发表时间：
2009-04-01
影响因子：
4.5
作者：
Gayer, Christopher P.;Chaturvedi, Lakshmi S.;Basson, Marc D.
通讯作者：
Basson, Marc D.
影响因子：
2.2
作者：
Kovalenko, Pavlo L.;Basson, Marc D.
通讯作者：
Basson, Marc D.
影响因子：
--
作者：
BROWN, HO;LEVINE, ML;LIPKIN, M
通讯作者：
LIPKIN, M