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Methionine Restriction and Modification of Epithelial Tight Junction Barrier Function and Permeability

机译:蛋氨酸的限制和上皮紧密连接屏障功能和通透性的修改

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It is well known that caloric restriction leads to an increased longevity by forestalling age-related diseases.Dietary restriction of methionine also renders similar benefits. In this review, we report studies on the effect of methioninerestriction on epithelial barrier function in a renal epithelial LLC-PK1 cell, a rodent gastrointestinal model and a clinicaltrial using Crohn’s patients. In LLC-PK1 cell culture, a reduction of culture medium methionine by 80% resulted inaltered tight junctional claudin composition with improved epithelial barrier function as exemplified by increased transepithelialelectrical resistance and decreased paracellular leak to 14C-D-mannitol. In addition to small but significantreductions in plasma and intracellular colonocyte methionine levels, dietary methionine restriction tightens intestinalepithelium and reduces mannitol permeability in rat colonic, but not ileal tissue. Crohn’s patients on methionine-restricteddiet reported improved symptoms as demonstrated by a reduced CDAI index, but this diet was not able to significantlyreduce the plasma methionine level in patients recruited. An increased urinary lactulose/mannitol ratio was also the resultof the regimen in Crohn’s patients, suggesting an increased, rather than decreased ileal leakage. Overall, our resultsshowed that reduction in dietary intake of methionine is promising in improving at least some epithelial barriers and thismay be through altering tight junctional protein compositions. Methionine restriction might result in contrasting effectsdepending on the tissue type and possible disease conditions, thus wider range of studies are required.
机译:众所周知,热量限制可预防与年龄有关的疾病,从而延长寿命。蛋氨酸的饮食限制也有类似的益处。在这篇综述中,我们报道了使用克罗恩病患者的蛋氨酸限制对肾上皮LLC-PK1细胞,啮齿动物胃肠道模型和临床试验的上皮屏障功能的影响的研究。在LLC-PK1细胞培养物中,将蛋氨酸的培养基减少80%会导致紧密连接的claudin组成发生改变,并具有上皮屏障功能的改善,例如跨上皮电阻抗的增加和细胞旁向14C-D-甘露醇的泄漏的减少。除了使血浆和细胞内结肠细胞蛋氨酸水平小幅但显着降低外,饮食中蛋氨酸的限制还会使肠道上皮变紧,并降低大鼠结肠(但不是回肠组织)中的甘露醇通透性。克罗恩限制蛋氨酸饮食的患者报告症状改善,CDAI指数降低,但这种饮食不能显着降低新招募患者的血浆蛋氨酸水平。克罗恩病患者的治疗方案还导致尿中乳果糖/甘露醇比例的增加,这表明回肠漏液的增加而不是减少。总的来说,我们的结果表明,减少蛋氨酸的饮食摄入有望改善至少一些上皮屏障,这可能是通过改变紧密的连接蛋白组成。蛋氨酸的限制取决于组织类型和可能的疾病状况可能会产生不同的效果,因此需要更广泛的研究。

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