The jagged-2/notch-1/hes-1 pathway is involved in intestinal epithelium regeneration after intestinal ischemia-reperfusion injury.
The jagged-2/notch-1/hes-1 pathway is involved in intestinal epithelium regeneration after intestinal ischemia-reperfusion injury.
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Jagged-2/Notch-1/Hes-1 通路参与肠缺血再灌注损伤后肠上皮再生
DOI：
10.1371/journal.pone.0076274
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Yang H
中科院分区：
文献类型：
--
作者：
Chen G;Qiu Y;Sun L;Yu M;Wang W;Xiao W;Yang Y;Liu Y;Yang S;Teitelbaum DH;Ma Y;Lu D;Yang H
Notch信号在肠隐窝上皮细胞增殖的维持中起关键作用。本研究旨在探讨Notch信号在肠缺血再灌注（I/R）损伤后肠上皮细胞增殖和再生中的作用。方法雄性Sprague-Dawley大鼠假手术或闭锁肠系膜上动脉（SMA） 20 min。于再灌注后0、1、2、4、6 h采集肠组织标本。采用增殖核抗原（PCNA）免疫组化染色评价肠上皮细胞的增殖情况。采用Real-time PCR和Western blot检测Notch信号组分的mRNA和蛋白表达水平。免疫荧光法检测Jagged-2、cleaved Notch-1和Hes-1在肠道中的表达和位置。最后，利用γ-分泌酶抑制剂DAPT和Jagged-2和Hes-1的siRNA，在体外IEC-6培养系统中研究Notch信号在肠上皮细胞增殖中的功能作用。结果I/R损伤引起肠隐窝上皮细胞增殖增加，Jagged-2、Notch-1、Hes-1 mRNA和蛋白表达增加。免疫荧光结果进一步证实肠隐窝Jagged-2、cleaved Notch-1和Hes-1蛋白表达增加。DAPT抑制Notch信号以及siRNA抑制Jagged-2和Hes-1的表达均能显著抑制IEC-6细胞的增殖。结论Jagged-2/Notch-1/Hes-1信号通路通过促进隐窝上皮细胞增殖参与I/R损伤后早期肠上皮再生。
Background Notch signaling plays a critical role in the maintenance of intestinal crypt epithelial cell proliferation. The aim of this study was to investigate the role of Notch signaling in the proliferation and regeneration of intestinal epithelium after intestinal ischemia reperfusion (I/R) injury. Methods Male Sprague-Dawley rats were subjected to sham operation or I/R by occlusion of the superior mesenteric artery (SMA) for 20 min. Intestinal tissue samples were collected at 0, 1, 2, 4, and 6 h after reperfusion. Proliferation of the intestinal epithelium was evaluated by immunohistochemical staining of proliferating nuclear antigen (PCNA). The mRNA and protein expression levels of Notch signaling components were examined using Real-time PCR and Western blot analyses. Immunofluorescence was also performed to detect the expression and location of Jagged-2, cleaved Notch-1, and Hes-1 in the intestine. Finally, the γ-secretase inhibitor DAPT and the siRNA for Jagged-2 and Hes-1 were applied to investigate the functional role of Notch signaling in the proliferation of intestinal epithelial cells in an in vitro IEC-6 culture system. Results I/R injury caused increased intestinal crypt epithelial cell proliferation and increased mRNA and protein expression of Jagged-2, Notch-1, and Hes-1. The immunofluorescence results further confirmed increased protein expression of Jagged-2, cleaved Notch-1, and Hes-1 in the intestinal crypts. The inhibition of Notch signaling with DAPT and the suppression of Jagged-2 and Hes-1 expression using siRNA both significantly inhibited the proliferation of IEC-6 cells. Conclusion The Jagged-2/Notch-1/Hes-1 signaling pathway is involved in intestinal epithelium regeneration early after I/R injury by increasing crypt epithelial cell proliferation.
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影响因子：
15.9
作者：
FUJIMOTO, K;IMAMURA, I;TSO, P
通讯作者：
TSO, P
影响因子：
10.5
作者：
BAILEY, AM;POSAKONY, JW
通讯作者：
POSAKONY, JW
影响因子：
5.3
作者：
Murata, K;Hattori, M;Minato, N
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影响因子：
3.7
作者：
Cai Y;Wang W;Liang H;Sun L;Teitelbaum DH;Yang H
通讯作者：
Yang H
影响因子：
7.7
作者：
Riccio, Orbicia;van Gijn, Marielle E.;Radtke, Freddy
通讯作者：
Radtke, Freddy