Beauchamp R D, Barnard J A, McCutchen C M, Cherner J A, Coffey R J
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
J Clin Invest. 1989 Sep;84(3):1017-23. doi: 10.1172/JCI114223.
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.
转化生长因子α（TGFα）与表皮生长因子（EGF）具有结构同源性（35%），拥有共同的细胞表面膜受体（TGFα/EGF受体），并且具有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TGFα mRNA在成年豚鼠、大鼠和犬的正常胃黏膜中的表达情况。在10例患者手术切除的匹配胃黏膜及相邻胃癌组织中，以及在另外1例患者良性溃疡旁的胃黏膜中也检测到了TGFα mRNA。通过放射免疫测定法定量TGFα蛋白，发现其存在于肿瘤及相邻黏膜中。在所有研究的物种的胃黏膜中也检测到了TGFα/EGF受体mRNA。在未分级的豚鼠胃黏膜样本以及富含主细胞和富含壁细胞的组分中检测了TGFα和TGFα/EGF受体mRNA表达的定位。所有样本均表现出TGFα和TGFα/EGF受体表达。相对于未分级的胃黏膜，TGFα信号在壁细胞组分中最强（增加了5.8倍），但在主细胞组分中也有所增强（增加了1.9倍）。与TGFα表达情况类似，相对于未分级的豚鼠胃黏膜，TGFα/EGF受体mRNA表达在富含壁细胞的组分中最为强烈（增加了7.8倍），但在富含主细胞的组分中也有所增加（增加了2.7倍）。我们得出结论，TGFα和TGFα/EGF受体基因在正常成年哺乳动物胃黏膜中表达。根据TGFα和EGF已描述的作用来解释这些发现，为TGFα的局部产生可能在胃的酸分泌调节和黏膜更新中发挥重要作用提供了证据。
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