Stimulation of gastric ulcer healing by heat shock protein 70
Stimulation of gastric ulcer healing by heat shock protein 70
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DOI：
10.1016/j.bcp.2011.06.030
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发表时间：
2011-10-01
影响因子：
5.8
通讯作者：
Mizushima, Tohru
中科院分区：
文献类型：
--
作者：
Ishihara, Tomoaki;Suemasu, Shintaro;Mizushima, Tohru
在胃溃疡的治疗中，不仅要防止进一步的溃疡形成，而且要促进溃疡的愈合。当细胞暴露在胃刺激物中时，热休克蛋白(HSPs)的表达被诱导，使细胞对刺激物具有抵抗力。我们最近报道了直接证据表明，热休克蛋白，特别是热休克蛋白70，可以预防刺激性胃溃疡的形成。胃溃疡愈合是胃溃疡边缘细胞增殖、迁移和肉芽组织血管生成的过程。在这项研究中，我们研究了HSP70在胃溃疡愈合中的作用。采用局部和浆膜外用冰醋酸的方法造成胃溃疡。HSP70在胃溃疡边缘和肉芽组织中均有表达。与野生型小鼠相比，表达HSP70的转基因小鼠胃溃疡愈合速度加快，胃溃疡边缘细胞增殖和肉芽组织血管生成均增强。在溃疡形成之前或之后，给野生型小鼠口服热休克蛋白的诱导剂香叶基香叶内酮，不仅能诱导胃中热休克蛋白70的表达，还能加速胃溃疡的愈合。另一方面，在溃疡形成前口服纯化的重组HSP70，而不是在溃疡形成后口服，可促进胃溃疡愈合。这项研究首次提供了HSP70加速胃溃疡愈合的证据。结果还表明，在溃疡形成之前产生并从受损细胞释放的HSP70，以及在溃疡形成后产生的HSP70都参与了这种加速愈合的过程。(C)2011 Elsevier Inc.保留所有权利。
It is important in treatment of gastric ulcers to not only prevent further ulcer formation but also enhance ulcer healing. When cells are exposed to gastric irritants, expression of heat shock proteins (HSPs) is induced, making the cells resistant to the irritants. We recently reported direct evidence that HSPs, especially HSP70, are preventive against irritant-induced gastric ulcer formation. Gastric ulcer healing is a process involving cell proliferation and migration at the gastric ulcer margin and angiogenesis in granulation tissue. In this study, we have examined the role of HSP70 in gastric ulcer healing. Gastric ulcers were produced by focal and serosal application of acetic acid. Expression of HSP70 was induced in both the gastric ulcer margin and granulation tissue. Compared with wild-type mice, gastric ulcer healing was accelerated in transgenic mice expressing HSP70, and both cell proliferation at the gastric ulcer margin and angiogenesis in granulation tissue were enhanced. Oral administration of geranylgeranylacetone, an inducer of HSPs, to wild-type mice, either prior to or after ulcer formation, not only induced expression of HSP70 in the stomach but also accelerated gastric ulcer healing. On the other hand, oral administration of purified recombinant HSP70 prior to the ulcer formation, but not after formation, stimulated gastric ulcer healing. This study provides the first evidence that HSP70 accelerates gastric ulcer healing. The results also suggest that both the HSP70 produced prior to ulcer formation and released from damaged cells, and the HSP70 produced after ulcer formation are involved in this accelerated healing process. (C) 2011 Elsevier Inc. All rights reserved.