Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Sci Rep. 2019 Mar 26;9(1):5199. doi: 10.1038/s41598-019-41604-4.
Endoplasmic reticulum (ER) stress in beta cells is an important pathogenic component of both type 1 and type 2 diabetes mellitus, as well as genetic forms of diabetes, especially Wolfram syndrome. However, there are currently no convenient ways to assess ER stress in beta cells, raising the need for circulating ER stress markers indicative of beta cell health. Here we show that pancreatic stone protein/regenerating protein (PSP/reg) is a potential biomarker for ER stressed beta cells. PSP/reg levels are elevated in cell culture and mouse models of Wolfram syndrome, a prototype of ER stress-induced diabetes. Moreover, PSP/reg expression is induced by the canonical chemical inducers of ER stress, tunicamycin and thapsigargin. Circulating PSP/reg levels are also increased in some patients with Wolfram syndrome. Our results therefore reveal PSP/reg as a potential biomarker for beta cells under chronic ER stress, as is the case in Wolfram syndrome.
内质网（ER）应激在β细胞中是 1 型和 2 型糖尿病以及遗传形式的糖尿病的重要发病成分，特别是 W olfram 综合征。然而，目前没有方便的方法来评估β细胞中的 ER 应激，这就需要有循环的 ER 应激标志物来指示β细胞的健康状况。在这里，我们表明胰腺结石蛋白/再生蛋白（PSP/reg）是 ER 应激β细胞的潜在生物标志物。PSP/reg 水平在 W olfram 综合征的细胞培养和小鼠模型中升高，W olfram 综合征是 ER 应激诱导型糖尿病的原型。此外，PSP/reg 的表达是由经典的 ER 应激化学诱导剂衣霉素和 thapsigargin 诱导的。循环 PSP/reg 水平在一些 W olfram 综合征患者中也升高。因此，我们的结果揭示了 PSP/reg 作为慢性 ER 应激下β细胞的潜在生物标志物，就像 W olfram 综合征一样。
