Early changes in the urine proteome in a diethyldithiocarbamate-induced chronic pancreatitis rat model

Abstract

Without homeostasis mechanisms, urine accumulates early changes in biomarkers and can be a better and earlier biomarker source than blood, especially for chronic diseases. This study tests whether early changes can be detected in a rat model of chronic pancreatitis induced by intraperitoneal injection of diethyldithiocarbamate. Urinary proteins from three rats were profiled by liquid chromatography coupled with tandem mass spectrometry. Compared with before injection, fifty differential proteins that had human orthologs were significantly changed in the chronic pancreatitis rats. At week 2, fifteen differential proteins were identified when no obvious pathological changes had yet appeared. Among them, twelve proteins were altered at the other two time points, five had previously been associated with chronic pancreatitis. Inflammatory cytokines infiltration, acinar disruption and fibrosis were detected at week 3 and week 4, at which points fourteen identified differential proteins had been reported to be differentially expressed in the serum or pancreatic tissue of chronic pancreatitis patients and other animal model studies. These include proteins that are significant in acute-phase response (FETUA, F2, FINC and REG3G), extracellular matrix organization (COMP, FINC) and tissue remodeling (CSPG4, GAS6). REG3G has been described abnormally expressed in several human digestive system diseases such as chronic pancreatitis. SignificanceThis study demonstrate that changes caused by chronic pancreatitis can be reflected early in urinary proteins. New clues for the early diagnosis of chronic pancreatitis can be found even with only the small number of model animals used.