MZB1 regulates cellular proliferation, mitochondrial dysfunction, and inflammation and targets the PI3K-Akt signaling pathway in acute pancreatitis

作者：Mengtao Xu, Yong Feng, Xuelian Xiang, Li Liu, Guodu Tang · 发表于：Cellular Signalling · 年份：2024 · DOI：10.1016/j.cellsig.2024.111143 · 被引用次数：18 · 研究领域：Pancreatitis Pathology and Treatment、Pancreatic and Hepatic Oncology Research、Amyloidosis: Diagnosis, Treatment, Outcomes

BACKGROUND: Acute pancreatitis (AP) is a pathological condition characterized by the premature release and activation of trypsinogens and other enzyme precursors. In severe cases, the mortality rates are in the range of 20-30% and may even be as high as 50%. Though various prophylaxes are available for AP, the mechanism of its progression is unclear. Marginal zone B and B-1 cell-specific protein 1 (MZB1) is found in the endoplasmic reticulum (ER) where it is expressed exclusively in the B cells there. MZB1 promotes proliferation, inhibits apoptosis, invasion, and inflammation, and mitigates mitochondrial damage in cells. However, the importance of MZB1 in AP has not yet been determined. METHODS: Differentially expressed genes (DEGs) between healthy pancreatic cells and those affected by AP were identified using datasets from Gene Expression Omnibus (GEO) datasets. Relative differences in MZB1 expression between normal and diseased tissues and cells were validated in vivo using a rat AP model induced with 4% (w/v) sodium taurocholate and in vitro using the AR42J rat pancreatic cell line exposed to caerulein (CAE). Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2`-deoxyuridine (EdU) assays were performed to detect and compare normal and pathological cell proliferation. Flow cytometry was employed to assess and compare cellular apoptosis. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot (WB) were applied to evaluate the apoptotic factors Bax and...