Abstract
Ubiquitin-specific protease 25 (USP25) plays an important role in inflammation and immunity. However, the role of USP25 in acute pancreatitis (AP) is still unclear. To evaluate the role of USP25 in AP, we conducted research on clinical AP patients, USP25wild-type(WT)/USP25 knockout (USP25−/−) mice, and pancreatic acinar cells. Our results showed that serum USP25 concentration was higher in AP patients than in healthy controls and was positively correlated with disease severity. AP patients’ serum USP25 levels after treatment were significantly lower than that at the onset of AP. Moreover, USP25 expression was upregulated in cerulein-induced AP in mice, while USP25 deficiency attenuates AP and AP-related multiple organ injury. In vivo and in vitro studies showed that USP25 exacerbates AP by promoting the release of pro-inflammatory factors and destroying tight junctions of the pancreas. We showed that USP25 aggravates AP and AP-related multiple organ injury by activating the signal transducer and activator of transcription 3 (STAT3) pathway. Targeting the action of USP25 may present a potential therapeutic option for treating AP.
Highlights
Acute pancreatitis (AP) is characterized by autodigestion, edema, hemorrhage, and even necrosis of the pancreatic tissue after activation of pancreatin
We collected clinical data from 79 patients diagnosed with acute pancreatitis (AP) (27 mild acute pancreatitis (MAP) patients, 34 moderate severe acute pancreatitis (MSAP) patients, and 18 severe acute pancreatitis (SAP) patients) and 53 healthy controls, and serum Ubiquitin-specific protease 25 (USP25), IL-6, tumor necrosis factor (TNF)-α, and IL-1β levels in AP patients and healthy controls were detected by enzymelinked immunosorbent assay (ELISA)
Our results show that serum USP25 is highly expressed in patients with AP and is positively correlated with inflammation and organ injury
Summary
Acute pancreatitis (AP) is characterized by autodigestion, edema, hemorrhage, and even necrosis of the pancreatic tissue after activation of pancreatin. Inflammation of the pancreas with or without organ failure can be observed during the course of pancreatitis. AP can be classified according to severity into mild acute pancreatitis (MAP), moderate severe acute pancreatitis (MSAP), and severe. USP25 Aggravates Acute Pancreatitis acute pancreatitis (SAP) (Crockett et al, 2018). 20% of AP patients develop SAP, which is related to systemic inflammatory response and multiple organ injury. Liver, kidney, and heart are organs that are often involved in AP-related multiple organ failure (Schepers et al, 2019). The incidence of acute pancreatitis is 34 cases per 100,000 persons each year with a 95% confidence interval [23.33, 48.81], and the mortality rate is 1.60 cases per 100,000 persons each year with a 95% confidence interval [0.85, 1.58] (Xiao et al, 2016). There is still no effective method to prevent AP
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