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首页> 外文期刊>American Journal of Physiology >Larazotide acetate: a pharmacological peptide approach to tight junction regulation
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Larazotide acetate: a pharmacological peptide approach to tight junction regulation

机译：幼虫醋酸盐：粘性接线调节的药理肽方法

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摘要

Larazotide acetate (LA) is a single-chain peptide of eight amino acids that acts as a tight junction regulator to restore intestinal barrier function. LA is currently being studied in phase III clinical trials and is orally administered to adult patients with celiac disease as an adjunct therapeutic to enhance intestinal barrier function that has been disrupted by gliadin-induced immune reactivity. Mechanistically, LA is thought to act as a zonulin antagonist to reduce zonulin-induced increases in barrier permeability and has been associated with the redistribution and rearrangement of tight junction proteins and actin filaments to restore intestinal barrier function. More recently, LA has been linked to inhibition of myosin light chain kinase, which likely reduces tension on actin filaments, thereby facilitating tight junction closure. Small (rodent) and large (porcine) animal studies have been conducted that demonstrate the importance of LA as a tight junction regulatory peptide in conditions other than celiac disease, including collagen-induced arthritis in mice and intestinal ischemic injury in pigs.
机译：醋酸拉唑肽（LA）是一种由八个氨基酸组成的单链肽，作为紧密连接调节剂来恢复肠道屏障功能。LA目前正在III期临床试验中进行研究，并被口服给患有乳糜泻的成年患者，作为一种辅助疗法，以增强因醇溶蛋白诱导的免疫反应而破坏的肠道屏障功能。从机制上讲，LA被认为是zonulin拮抗剂，可减少zonulin诱导的屏障通透性增加，并与紧密连接蛋白和肌动蛋白丝的重新分布和重排有关，以恢复肠道屏障功能。最近，LA与肌球蛋白轻链激酶的抑制有关，这可能会降低肌动蛋白丝的张力，从而促进紧密连接的闭合。已经进行了小型（啮齿类）和大型（猪）动物研究，证明了LA作为紧密连接调节肽在非乳糜泻条件下的重要性，包括小鼠胶原诱导的关节炎和猪的肠缺血损伤。

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