Heparin-binding EGF-like growth factor protects intestinal stem cells from injury in a rat model of necrotizing enterocolitis.
Heparin-binding EGF-like growth factor protects intestinal stem cells from injury in a rat model of necrotizing enterocolitis.
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DOI：
10.1038/labinvest.2011.167
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发表时间：
2012-03
期刊：
影响因子：
--
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中科院分区：
文献类型：
--
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坏死性小肠结肠炎 (NEC) 是一种通常影响早产新生儿的灾难性疾病。尽管 NEC 的确切病因尚不清楚，但该疾病与配方奶喂养、肠道细菌定植、缺氧和灌注不足有关。鉴于NEC的发病机制，肠粘膜的完整性和功能对于NEC的发生起着重要的防御作用。包括 NEC 在内的各种形式的肠道损伤会损伤肠上皮细胞 (IEC) 谱系，包括肠干细胞 (ISC)，从而破坏维持肠道屏障功能所需的正常稳态。在当前的研究中，我们研究了 HB-EGF 给药对实验性 NEC 新生大鼠模型中肠上皮细胞、杯状细胞、神经内分泌细胞和肠道干细胞的影响。我们还在体外细胞培养物和离体隐窝绒毛类器官培养物中检测了肝素结合 EGF 样生长因子 (HB-EGF) 对肠干细胞的细胞保护作用。我们发现 HB-EGF 可以保护所有肠上皮细胞谱系（包括肠干细胞）免受损伤。我们进一步发现，HB-EGF 在体外保护分离的肠干细胞免受缺氧损伤，并在离体隐窝绒毛类器官培养物中促进肠干细胞活化和存活以及隐窝转运扩增细胞的扩增。 HB-EGF 的保护作用取决于 EGF 受体的激活，并通过 MEK1/2 和 PI3K 信号通路介导。这些结果表明，HB-EGF 的肠道细胞保护作用至少部分是通过其保护肠道干细胞免受损伤的能力来介导的。
Necrotizing enterocolitis (NEC) is an often catastrophic disease that typically affects premature newborns. Although the exact etiology of NEC is uncertain, the disease is associated with formula feeding, bacterial colonization of the gut, hypoxia, and hypoperfusion. In light of the pathogenesis of NEC, the integrity and function of the intestinal mucosa plays a major defensive role against the initiation of NEC. Various forms of intestinal injury, including NEC, injure the intestinal epithelial cell (IEC) lineages, including the intestinal stem cells (ISCs), thereby disrupting the normal homeostasis needed to maintain gut barrier function. In the current study we examined the effects of HB-EGF administration on enterocytes, goblet cells, neuroendocrine cells and intestinal stem cells in a newborn rat model of experimental NEC. We also examined the cytoprotective effects of heparin-binding EGF-like growth factor (HB-EGF) on intestinal stem cells in in vitro cell cultures and in ex vivo crypt-villous organoid cultures. We found that HB-EGF protects all intestinal epithelial cell lineages, including intestinal stem cells, from injury. We further found that HB-EGF protects isolated intestinal stem cells from hypoxic injury in vitro, and promotes intestinal stem cell activation and survival, and the expansion of crypt transit amplifying cells, in ex vivo crypt-villous organoid cultures. The protective effects of HB-EGF were dependent upon EGF receptor activation, and were mediated via the MEK1/2 and PI3K signaling pathways. These results demonstrate that the intestinal cytoprotective effects of HB-EGF are mediated, at least in part, through its ability to protect intestinal stem cells from injury.
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影响因子：
29.4
作者：
Dekaney, CM;Rodriguez, JM;Henning, SJ
通讯作者：
Henning, SJ
影响因子：
4.8
作者：
Cetin, S;Ford, HR;Hackam, DJ
通讯作者：
Hackam, DJ
影响因子：
3.1
作者：
BESNER, GE;KLAGSBRUN, M
通讯作者：
KLAGSBRUN, M
在肠肠上细胞中过表达肝素结合EGF的生长因子转基因的小鼠中的肠表型。
DOI：
10.3109/08977190903407365
发表时间：
2010-04
期刊：
Growth factors (Chur, Switzerland)
影响因子：
--
作者：
Chen CL;Mehta VB;Zhang HY;Wu D;Otabor I;Radulescu A;El-Assal ON;Feng J;Chen Y;Besner GE
通讯作者：
Besner GE
影响因子：
1.7
作者：
Feng, Jiexiong;El-Assal, Osama N;Besner, Gail E
通讯作者：
Besner, Gail E