Background & Aims

The intestinal epithelium must be resilient to physiochemical stress to uphold the physiological barrier separating the systemic compartment from the microbial and antigenic components of the gut lumen. Identifying proteins that mediate protection and enhancing their expression is therefore a clear approach to promote intestinal health. We previously reported that oral ingestion of the probiotic Lactobacillus rhamnosus GG not only induced the expression of several recognized cytoprotective factors in the murine colon, but also many genes with no previously described function, including the gene encoding proline-rich acidic protein 1 (PRAP1). PRAP1 is a highly expressed protein in the epithelium of the gastrointestinal tract and we sought to define its function in this tissue.

Methods

Purified preparations of recombinant PRAP1 were analyzed biochemically and PRAP1 antisera were used to visualize localization in tissues. Prap1^-/- mice were characterized at baseline and challenged with total body irradiation, then enteroids were generated to recapitulate the irradiation challenge ex vivo.

Results

PRAP1 is a 17-kilodalton intrinsically disordered protein with no recognizable sequence homology. PRAP1 expression levels were high in the epithelia of the small intestine. Although Prap1^-/- mice presented only mild phenotypes at baseline, they were highly susceptible to intestinal injury upon challenge. After irradiation, the Prap1^-/- mice showed accelerated death with a significant increase in apoptosis and p21 expression in the small intestinal epithelium.

Conclusions

PRAP1 is an intrinsically disordered protein highly expressed by the gastrointestinal epithelium and functions at exposed surfaces to protect the barrier from oxidative insult.

中文翻译：

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富含脯氨酸的酸性蛋白 1 (PRAP1) 保护胃肠上皮免受辐射诱导的细胞凋亡。

背景与目标

肠上皮必须对生理化学应激有弹性，以维持将系统区室与肠腔的微生物和抗原成分分开的生理屏障。因此，鉴定介导保护和增强其表达的蛋白质是促进肠道健康的明确方法。我们之前曾报道，口服益生菌鼠李糖乳杆菌GG 不仅会诱导小鼠结肠中几种公认的细胞保护因子的表达，而且还会诱导许多先前没有描述功能的基因的表达，包括编码富含脯氨酸的酸性蛋白 1 (PRAP1) 的基因. PRAP1 是胃肠道上皮中高度表达的蛋白质，我们试图确定其在该组织中的功能。

方法

重组 PRAP1 的纯化制剂进行生化分析，PRAP1 抗血清用于可视化组织中的定位。Prap1 ^-/-小鼠在基线时被表征并接受全身照射挑战，然后产生肠体以概括体外照射挑战。

结果

PRAP1 是一种 17 千道尔顿固有无序蛋白质，没有可识别的序列同源性。PRAP1 表达水平在小肠的上皮细胞中很高。尽管Prap1 ^-/-小鼠在基线时仅表现出轻微的表型，但它们在受到攻击时极易受到肠道损伤。照射后，Prap1 ^-/-小鼠表现出加速死亡，小肠上皮细胞凋亡和 p21 表达显着增加。

结论

PRAP1 是一种内在无序的蛋白质，由胃肠上皮细胞高度表达，在暴露的表面起作用以保护屏障免受氧化损伤。