LOCALIZATION OF TRANSFORMING GROWTH FACTOR-ALPHA AND ITS RECEPTOR IN GASTRIC-MUCOSAL CELLS - IMPLICATIONS FOR A REGULATORY ROLE IN ACID-SECRETION AND MUCOSAL RENEWAL
LOCALIZATION OF TRANSFORMING GROWTH FACTOR-ALPHA AND ITS RECEPTOR IN GASTRIC-MUCOSAL CELLS - IMPLICATIONS FOR A REGULATORY ROLE IN ACID-SECRETION AND MUCOSAL RENEWAL
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DOI：
10.1172/jci114223
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发表时间：
1989-09-01
影响因子：
15.9
通讯作者：
COFFEY, RJ
中科院分区：
文献类型：
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作者：
BEAUCHAMP, RD;BARNARD, JA;COFFEY, RJ
转化生长因子。（tgf . α）与表皮生长因子（EGF）具有结构同源性（35%），是一种常见的细胞膜受体（tgf . α）。/EGF受体)，以及几乎相同的生物活性谱，包括抑制胃酸分泌。在此，我们报道了TGF.alpha的表达。成年豚鼠、大鼠和狗正常胃粘膜mRNA的表达。TGF.alpha。在10例手术切除的胃粘膜和邻近胃癌患者以及另1例良性溃疡邻近胃粘膜中也检测到mRNA。TGF.alpha。用放射免疫法测定肿瘤及邻近粘膜中蛋白含量。TGF.alpha。在所有研究物种的胃粘膜中也检测到/EGF受体mRNA。tgf . α的定位。和TGF.alpha。/EGF受体mRNA在未分离的豚鼠胃粘膜、主要富集细胞和壁层富集细胞的样品中表达。所有样品均显示tgf . α。和TGF.alpha。/EGF受体表达。TGF.alpha。相对于未分离的胃粘膜，信号在壁细胞部分最大（增加5.8倍），但在主细胞部分也增强（增加1.9倍）。像TGF.alpha。表情,TGF.alpha。/EGF受体mRNA的表达在壁细胞富集部分最为强烈（增加了7.8倍），但在主要细胞富集部分也相对于未分离的豚鼠胃粘膜增加了（增加了2.7倍）。我们得出结论，tgf。和TGF.alpha。/EGF受体基因在正常成年哺乳动物胃粘膜中表达。这些发现，当解释了所描述的tgf . α的作用。和EGF，提供了tgf - α的局部产生的证据。可能在调节胃酸分泌和粘膜更新中起重要作用。
Transforming growth factor .alpha. (TGF.alpha.) shares with epidermal growth factor (EGF) structural homology (35%), a common cell-surface membrane receptor (TGF.alpha./EGF receptor), and a nearly identical spectrum of biological activity, including inhibition of gastric acid secretion. Herein, we report expression of TGF.alpha. mRNA in normal gastric mucosa of the adult guinea pig, rat, and dog. TGF.alpha. mRNA was also detected in matched surgically resected gastric mucosa and adjacent gastric carcinoma from 10 patients, and in gastric mucosa adjacent to a benign ulcer from an additional patient. TGF.alpha. protein was quantitated by radioimmunoassay and was present in tumor and adjacent mucosa. TGF.alpha./EGF receptor mRNA was also detected in gastric mucosa from all species studied. Localization of TGF.alpha. and TGF.alpha./EGF receptor mRNA expression was examined in samples of unfractionated guinea pig gastric mucosa and from chief cell-enriched and parietal cell-enriched fractions. All samples exhibited TGF.alpha. and TGF.alpha./EGF receptor expression. The TGF.alpha. signal was greatest in the parietal cell fraction (5.8-fold increase), but was also enhanced in the chief cell fraction (1.9-fold increase) relative to the unfractionated gastric mucosa. Like TGF.alpha. expression, TGF.alpha./EGF receptor mRNA expression was most intense in the parietal cell-enriched fraction (7.8-fold increase), but was also increased in the chief cell-enriched fraction (2.7-fold increase) relative to the unfractionated guinea pig gastric mucosa. We conclude that TGF.alpha. and TGF.alpha./EGF receptor genes are expressed in normal adult mammalian gastric mucosa. These findings, when interpreted in light of described actions of TGF.alpha. and EGF, provide evidence that local production of TGF.alpha. could play an important role in the regulation of acid secretion and mucosal renewal in the stomach.