Erin Nuray, Türker Sema, Elpek Özlem, Yildirim Bülent
Department of Medical Pharmacology, School of Medicine, Akdeniz University, Antalya 07070, Turkey.
Department of Internal Medicine, School of Medicine, Akdeniz University, Antalya 07070, Turkey.
Exp Ther Med. 2018 Feb;15(2):1999-2005. doi: 10.3892/etm.2017.5619. Epub 2017 Dec 12.
ADAM metallopeptidase domain (ADAM)9, 10 and 17 have α-secretase activity that regulates ectodomain shedding of factors involved in inflammation, cell proliferation, angiogenesis, and wound healing. The secretase activity of ADAM proteins is known to induce an inflammatory response. However, under certain conditions, a lack of secretase activity may induce inflammation suggesting differential roles of ADAM proteins with secretase activity. To the best of our knowledge, the present study evaluated the changes in α-secretase activity and expression of associated ADAM proteases (ADAM9, 10 and 17) in the gastric mucosa of patients with gastritis and ulcers, for the first time. Gastroduedonal mucosal samples from 42 patients were snap-frozen to determine changes in α-secretase activity. Twenty-four of these patients had gastritis, 9 patients had duedonal ulcers and 9 patients did not have any pathological changes. Paraffin-embedded gastric specimens (n=32) were used for immunohistochemical detection of ADAM9, ADAM10 and ADAM17. α-secretase activity of the gastric mucosa of healthy subjects was significantly higher compared with the uninvolved mucosa of patients with gastritis or ulcer. These results were associated with the immunohistochemical staining results, which demonstrated that ADAM10 expression markedly decreased in glandular epithelial cells and ADAM9 expression was lost in foveolar epithelial cells of gastric mucosa adjacent to ulcer. However, ADAM17 expression was increased in the normal gastric mucosa of patients with bleeding peptic ulcers and in the gastric mucosa adjacent to the ulcer suggesting a counteracting role of ADAM17. Decreased ADAM9 and 10 expression, and an associated decrease in α-secretase activity may predispose to chronic gastritis and ulcer. Further studies are required to determine the possible etiological role of increased ADAM17 expression.
ADAM金属蛋白酶结构域（ADAM）9、10和17具有α-分泌酶活性，可调节参与炎症、细胞增殖、血管生成和伤口愈合的因子的胞外域脱落。已知ADAM蛋白的分泌酶活性会诱导炎症反应。然而，在某些情况下，分泌酶活性的缺乏可能会诱发炎症，这表明具有分泌酶活性的ADAM蛋白具有不同的作用。据我们所知，本研究首次评估了胃炎和溃疡患者胃黏膜中α-分泌酶活性及相关ADAM蛋白酶（ADAM9、10和17）表达的变化。对42例患者的胃十二指肠黏膜样本进行速冻，以确定α-分泌酶活性的变化。其中24例患者患有胃炎，9例患者患有十二指肠溃疡，9例患者无任何病理变化。采用石蜡包埋的胃标本（n = 32）进行ADAM9、ADAM10和ADAM17的免疫组织化学检测。与胃炎或溃疡患者未受累的黏膜相比，健康受试者胃黏膜的α-分泌酶活性显著更高。这些结果与免疫组织化学染色结果相关，后者表明ADAM10在腺上皮细胞中的表达明显降低，而在溃疡附近胃黏膜的小凹上皮细胞中ADAM9表达缺失。然而，ADAM17在消化性溃疡出血患者的正常胃黏膜及溃疡附近的胃黏膜中表达增加，提示ADAM17具有抵消作用。ADAM9和10表达降低以及相关的α-分泌酶活性降低可能易患慢性胃炎和溃疡。需要进一步研究以确定ADAM17表达增加可能的病因学作用。
