Poulsom R
In Situ Hybridisation Service, Imperial Cancer Research Fund, London, UK.
Baillieres Clin Gastroenterol. 1996 Mar;10(1):113-34. doi: 10.1016/s0950-3528(96)90043-3.
There is a growing body of evidence supporting the hypothesis that members of the trefoil peptide family are involved actively in maintaining the integrity of the gastrointestinal mucosa and facilitating its repair. To date, three trefoil peptides are known in man: pS2, ITF and SP. Each is a secretory peptide expressed in specific compartments throughout the gut, in patterns that appear generally to be conserved between mammalian species. Ulceration, whether due to common pathological processes or experimentally induced, results in altered local expression of trefoil peptides. In diverse chronic ulcerative conditions in man, glandular structures develop within the mucosa, derived from the UACL. These UACL glands express three trefoil peptides, EGF and lysozyme, all potentially able to contribute to the healing process. In fact local goblet and endocrine cell types may also be recruited to secrete pS2 into the local environment. In experimental ulcers, in rate stomach or intestinal resection margins, there is also accentuation of trefoil peptide expression at the margins and in the poorly differentiated mucous cells extending out presumably in attempts to restore epithelial integrity. Several trefoil peptides have been expressed as 'recombinant' proteins in bacterial, baculoviral or yeast systems, and these procedures have allowed some of the biological properties of these peptides to be determined. In vitro, rITF, hITF and hSP are motogens, able to promote migration of epithelial cells. In vivo, rITF and hSP are able to prevent much of the gastric damage effect by a single dose of indomethacin, when given systemically. There is synergy between EGF and rITF both in vitro and in vivo, which may allow the development of new peptide therapies for ulceration that will maximize repair and minimize cell proliferation.
越来越多的证据支持这样一种假说，即三叶肽家族成员积极参与维持胃肠道黏膜的完整性并促进其修复。迄今为止，人类已知三种三叶肽：pS2、ITF和SP。每一种都是在整个肠道的特定区域表达的分泌性肽，其表达模式在哺乳动物物种之间通常是保守的。溃疡，无论是由于常见的病理过程还是实验诱导的，都会导致三叶肽的局部表达改变。在人类各种慢性溃疡性疾病中，黏膜内会形成源自UACL的腺结构。这些UACL腺表达三种三叶肽、表皮生长因子（EGF）和溶菌酶，它们都可能有助于愈合过程。事实上，局部杯状细胞和内分泌细胞类型也可能被募集来向局部环境中分泌pS2。在实验性溃疡中，在胃或肠切除边缘，三叶肽在边缘以及可能延伸出来试图恢复上皮完整性的低分化黏液细胞中的表达也会增强。几种三叶肽已在细菌、杆状病毒或酵母系统中表达为“重组”蛋白，这些方法使人们能够确定这些肽的一些生物学特性。在体外，重组ITF（rITF）、人ITF（hITF）和人SP是促细胞运动剂，能够促进上皮细胞迁移。在体内，当全身给药时，rITF和hSP能够预防单次剂量消炎痛造成的大部分胃损伤效应。在体外和体内，EGF与rITF之间都存在协同作用，这可能有助于开发新的溃疡肽疗法，使修复最大化并使细胞增殖最小化。
