Ubiquitin-Specific Protease 25 Aggravates Acute Pancreatitis and Acute Pancreatitis-Related Multiple Organ Injury by Destroying Tight Junctions Through Activation of The STAT3 Pathway

Zhengru Liu; Mingming Qi; Shan Tian; Qian Yang; Jian Liu; Siwei Wang; Mengyao Ji; Rong Yu; Suqi Zeng; Jinting Li; Yuping Wei; Weiguo Dong

doi:10.3389/fcell.2021.806850

Ubiquitin-Specific Protease 25 Aggravates Acute Pancreatitis and Acute Pancreatitis-Related Multiple Organ Injury by Destroying Tight Junctions Through Activation of The STAT3 Pathway

Front Cell Dev Biol. 2022 Jan 13:9:806850. doi: 10.3389/fcell.2021.806850. eCollection 2021.

Authors

Zhengru Liu¹, Mingming Qi¹, Shan Tian¹, Qian Yang¹, Jian Liu¹, Siwei Wang¹, Mengyao Ji¹, Rong Yu¹, Suqi Zeng¹, Jinting Li¹, Yuping Wei¹, Weiguo Dong¹

Affiliation

¹ Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China.

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, USP25^{wild-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.

Keywords: acute pancreatitis; multiple organ injury; signal transducer and activator of transcription 3 pathway; tight junctions; ubiquitin-specific protease 25.