Altered gastric chief cell lineage differentiation in histamine-deficient mice
Altered gastric chief cell lineage differentiation in histamine-deficient mice
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DOI：
10.1152/ajpgi.90643.2008
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发表时间：
2009-06-01
影响因子：
4.5
通讯作者：
Goldenring, James R.
中科院分区：
文献类型：
--
作者：
Nozaki, Koji;Weis, Victoria;Goldenring, James R.
王春华，王春华，王春华。组胺缺乏小鼠胃主细胞谱系分化的研究进展。[J] .中国生物医学工程学报，2009,31(6):1211- 1220。首次发表于2009年4月9日；doi: 10.1152 / ajpgi.90643.2008。-胃腺内细胞系的有序分化受局部粘膜生长因子和激素复杂的相互作用调节。肠嗜铬样细胞分泌的组胺不仅在刺激胃酸分泌中起重要作用，而且在协调粘膜内生长和谱系分化中起重要作用。我们研究了缺乏内源性组胺合成的组氨酸脱羧酶（HDC）缺陷小鼠，以评估组胺对急性氧合性萎缩诱导的基底粘膜谱系分化和化生发展的影响。在8周龄和12月龄时对hdl缺陷小鼠和野生型小鼠的胃进行评估。DMP-777给予6周龄小鼠口服1 ~ 14天。胃粘膜切片用Mist1、内在因子、H/ k - atp酶、三叶因子2 （TFF2）、嗜铬粒蛋白A和Ext1抗体和细胞周期标记物磷酸组蛋白H3抗体染色。在8周龄的hdl缺陷小鼠中，表达Mist1和内在因子的主要细胞显著增加。重要的是，mist1阳性的成熟主细胞出现在腺中部和基底腺基部，表明主细胞的过早分化。HDC和胃泌素双缺乏小鼠的基底腺主细胞呈正态分布。用DMP-777治疗hdc缺陷小鼠可导致壁细胞的缺失和粘膜细胞化生的加速和扩大，在整个腺体长度上存在双内在因子和表达tff2的细胞，表明主细胞出现了表达spasmolytic多肽的化生（SPEM）。这些发现表明，组胺与胃泌素协同作用，调节主要细胞从粘膜颈细胞向基底腺迁移的适当分化。然而，急性氧合性萎缩后出现SPEM并不需要组胺。
Nozaki K, Weis V, Wang TC, Falus A, Goldenring JR. Altered gastric chief cell lineage differentiation in histamine-deficient mice. Am J Physiol Gastrointest Liver Physiol 296: G1211-G1220, 2009. First published April 9, 2009; doi:10.1152/ajpgi.90643.2008.-The orderly differentiation of cell lineages within gastric glands is regulated by a complicated interplay of local mucosal growth factors and hormones. Histamine secreted from enterochromaffin-like cells plays an important role in not only stimulated gastric acid secretion but also coordination of intramucosal growth and lineage differentiation. We have examined histidine-decarboxylase (HDC)-deficient mice, which lack endogenous histamine synthesis, to evaluate the influence of histamine on differentiation of fundic mucosal lineages and the development of metaplasia following induction of acute oxyntic atrophy. Stomachs from HDC-deficient mice and wild-type mice were evaluated at 8 wk and 12 mo of age. DMP-777 was administrated orally to 6-wk-old mice for 1 to 14 days. Sections of gastric mucosa were stained with antibodies against Mist1, intrinsic factor, H/K-ATPase, trefoil factor 2 (TFF2), chromogranin A, and Ext1 and for the cell cycle marker phospho-histone H3. HDC-deficient mice at 8 wk of age demonstrated a prominent increase in chief cells expressing Mist1 and intrinsic factor. Importantly Mist1-positive mature chief cells were present in the midgland region as well as at the bases of fundic glands, indicating a premature differentiation of chief cells. Mice dually deficient for both HDC and gastrin showed a normal distribution of chief cells in fundic glands. Treatment of HDC-deficient mice with DMP-777 led to loss of parietal cells and an accelerated and exaggerated emergence of mucous cell metaplasia with the presence of dual intrinsic factor and TFF2-expressing cells throughout the gland length, indicative of the emergence of spasmolytic polypeptide-expressing metaplasia (SPEM) from chief cells. These findings indicate that histamine, in concert with gastrin, regulates the appropriate differentiation of chief cells from mucous neck cells as they migrate toward the bases of fundic glands. Nevertheless, histamine is not required for emergence of SPEM following acute oxyntic atrophy.