The Development of Spasmolytic Polypeptide/TFF2-Expressing Metaplasia (SPEM) During Gastric Repair Is Absent in the Aged Stomach.
The Development of Spasmolytic Polypeptide/TFF2-Expressing Metaplasia (SPEM) During Gastric Repair Is Absent in the Aged Stomach.
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DOI：
10.1016/j.jcmgh.2016.05.004
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发表时间：
2016-09
影响因子：
7.2
通讯作者：
Zavros Y
中科院分区：
文献类型：
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作者：
Engevik AC;Feng R;Choi E;White S;Bertaux-Skeirik N;Li J;Mahe MM;Aihara E;Yang L;DiPasquale B;Oh S;Engevik KA;Giraud AS;Montrose MH;Medvedovic M;Helmrath MA;Goldenring JR;Zavros Y
在衰老过程中，胃的生理变化会导致胃组织更加纤细，修复损伤的能力较差，从而增加对慢性溃疡的易感性。胃壁细胞缺失和幽门螺杆菌感染后可出现表达痉挛多肽/三叶因子2的化生(SPEM)，但其在胃溃疡修复中的作用尚不清楚。因此，我们试图研究SPEM是否在上皮再生中起作用。以幼龄(2~3mo)和老龄(18~24mo)C57BL/6小鼠为研究对象，建立醋酸溃疡模型，观察溃疡修复质量随年龄增长的变化。用黄色变色龙3.0小鼠产生黄色荧光蛋白表达的有机物进行移植。诱导溃疡后，立即将黄色荧光蛋白阳性的胃有机物质移植到胃黏膜下层和胃腔内。收集并分析胃组织，以确定器官衍生细胞在再生上皮内的植入情况。年轻小鼠的伤口愈合与溃烂区域内SPEM的出现相吻合，这种反应在老年胃中是不存在的。尽管老年小鼠溃疡组织周围的化生较少，但器官移植的老年小鼠显示出再生的胃腺，其中包含有机衍生细胞。老龄小鼠器官移植可导致SPEM的出现和胃再生。这些数据显示了胃修复过程中SPEM的发展，以应对老年人胃中缺乏的损伤。此外，在损伤/移植小鼠模型中，胃有机化合物促进了胃再生。
During aging, physiological changes in the stomach result in more tenuous gastric tissue that is less capable of repairing injury, leading to increased susceptibility to chronic ulceration. Spasmolytic polypeptide/trefoil factor 2–expressing metaplasia (SPEM) is known to emerge after parietal cell loss and during Helicobacter pylori infection, however, its role in gastric ulcer repair is unknown. Therefore, we sought to investigate if SPEM plays a role in epithelial regeneration. Acetic acid ulcers were induced in young (2–3 mo) and aged (18–24 mo) C57BL/6 mice to determine the quality of ulcer repair with advancing age. Yellow chameleon 3.0 mice were used to generate yellow fluorescent protein–expressing organoids for transplantation. Yellow fluorescent protein–positive gastric organoids were transplanted into the submucosa and lumen of the stomach immediately after ulcer induction. Gastric tissue was collected and analyzed to determine the engraftment of organoid-derived cells within the regenerating epithelium. Wound healing in young mice coincided with the emergence of SPEM within the ulcerated region, a response that was absent in the aged stomach. Although aged mice showed less metaplasia surrounding the ulcerated tissue, organoid-transplanted aged mice showed regenerated gastric glands containing organoid-derived cells. Organoid transplantation in the aged mice led to the emergence of SPEM and gastric regeneration. These data show the development of SPEM during gastric repair in response to injury that is absent in the aged stomach. In addition, gastric organoids in an injury/transplantation mouse model promoted gastric regeneration.