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三叶肽对肠上皮屏障功能的保护作用:与黏蛋白糖蛋白的协同相互作用

Trefoil peptide protection of intestinal epithelial barrier function: cooperative interaction with mucin glycoprotein.

作者信息

Kindon H, Pothoulakis C, Thim L, Lynch-Devaney K, Podolsky D K

机构信息

Gastrointestinal Unit, Massachusetts General Hospital, Boston, USA.

出版信息

Gastroenterology. 1995 Aug;109(2):516-23. doi: 10.1016/0016-5085(95)90340-2.

DOI:10.1016/0016-5085(95)90340-2
PMID:7615201
Abstract

BACKGROUND & AIMS: Goblet cells secrete a combination of trefoil peptides and mucin glycoproteins to form a continuous gel on the mucosal surface. The functional effects of these products remain uncertain.

METHODS

Trefoil peptides and/or mucin glycoproteins were added to Transwell monolayers of the human colonic cancer-derived T84 cell line. Intact monolayers permitted penetration of < 4% of the inert marker [3H]mannitol at 4 hours. Exposure to the toxic lectin phytohemagglutinin (1 mg/mL), oleic acid (8 mmol/L) and taurocholic acid (12 mmol/L), or Clostridium difficile toxin A (0.7 microgram/mL) resulted in loss of barrier function with 36%, 62%, and 45% of [3H]mannitol penetration, respectively.

RESULTS

Addition of recombinant human intestinal trefoil factor in physiological concentrations (1-5 micrograms/microL) resulted in attenuation of the damage to monolayer integrity by up to 52%. Protection was enhanced (up to 95%) by the copresence of human colonic mucin glycoproteins. Similar effects were observed when rat intestinal trefoil factor or human spasmolysin, another human trefoil peptide, were added alone or in the presence of human mucin glycoproteins. Conversely, mucin glycoproteins isolated from the rat colon or stomach facilitated protection when added with human spasmolysin or human intestinal trefoil factor.

CONCLUSIONS

Trefoil peptides and mucin glycoproteins protect gastrointestinal mucosa from a variety of insults.

摘要

背景与目的

杯状细胞分泌三叶因子和黏蛋白糖蛋白的混合物,在黏膜表面形成连续的凝胶。这些产物的功能作用仍不确定。

方法

将三叶因子和/或黏蛋白糖蛋白添加到人结肠癌来源的T84细胞系的Transwell单层培养物中。完整的单层培养物在4小时时允许<4%的惰性标记物[3H]甘露醇穿透。暴露于毒性凝集素植物血凝素(1mg/mL)、油酸(8mmol/L)和牛磺胆酸(12mmol/L)或艰难梭菌毒素A(0.7μg/mL)会导致屏障功能丧失,[3H]甘露醇穿透率分别为36%、62%和45%。

结果

添加生理浓度(1 - 5μg/μL)的重组人肠三叶因子可使单层完整性损伤减轻高达52%。人结肠黏蛋白糖蛋白的共同存在可增强保护作用(高达95%)。单独添加或在人黏蛋白糖蛋白存在的情况下添加大鼠肠三叶因子或人解痉多肽(另一种人三叶因子)时,观察到类似的效果。相反,从大鼠结肠或胃中分离的黏蛋白糖蛋白与人类解痉多肽或人肠三叶因子一起添加时有助于保护作用。

结论

三叶因子和黏蛋白糖蛋白可保护胃肠道黏膜免受多种损伤。

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Trefoil peptide protection of intestinal epithelial barrier function: cooperative interaction with mucin glycoprotein.三叶肽对肠上皮屏障功能的保护作用:与黏蛋白糖蛋白的协同相互作用
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Identification of human intestinal trefoil factor. Goblet cell-specific expression of a peptide targeted for apical secretion.人肠三叶因子的鉴定。一种靶向顶端分泌的肽在杯状细胞中的特异性表达。
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