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Sci Rep. 2019 Mar 26;9(1):5199. doi: 10.1038/s41598-019-41604-4.

Pancreatic stone protein/regenerating protein is a potential biomarker for endoplasmic reticulum stress in beta cells.

Author information

1
Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, United States of America.
2
Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, Missouri, United States of America.
3
Division of Biology & Biomedical Sciences, Washington University School of Medicine, St. Louis, Missouri, United States of America.
4
MilliporeSigma (SAFC), St. Louis, Missouri, United States of America.
5
Department of Biochemistry, Institute of Biomedical & Health Science, Hiroshima University, Hiroshima, 734-8553, Japan.
6
Department of Visceral & Transplantation Surgery, University Hospital Zurich, Zurich, Switzerland.
7
Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
8
Departments of Psychiatry, Neurology, and Radiology, Washington University School of Medicine, St. Louis, Missouri, United States of America.
9
Department of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, Missouri, United States of America. urano@wustl.edu.
10
Deparment of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America. urano@wustl.edu.

Abstract

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.

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