Background Annexin A2 (ANXA2) plays a crucial role in acute pancreatitis (AP). However, its potential mechanism remains unclear. Methods In the present study, we used caerulein‐treated AR42J rat pancreatic acinar cells as cell model of AP to investigate the potential functions of ANXA2 and its predicted long noncoding RNA (lncRNA) FOXF1 adjacent noncoding developmental regulatory RNA (lncRNA Fendrr). Cell apoptosis was evaluated by flow cytometry using annexinV‐fluorescein isothiocyanate/propidium iodide staining. The expressions of ANAX2 and lncRNA Fendrr were detected by quantitative real‐time polymerase chain reaction (qRT‐PCR). Furthermore, Western blot analysis was performed to determine the protein levels of ANXA2, Bcl‐2, and Bax. The association between lncRNA Fendrr and ANXA2 was disclosed by RNA pull‐down, RNA immunoprecipitation, and electrophoretic mobility shift assays. Results ANXA2 was elevated in caerulein‐induced AP model and promoted apoptosis of AR42J cells. LncRNA Fendrr was also upregulated in AP cell model and directly bound ANXA2 protein. Further studies indicated that the interaction between ANXA2 and lncRNA Fendrr contributed to the apoptosis of AR42J cells in AP cell model. Conclusion Our study demonstrated that ANXA2 promoted AP progression via interacting with lncRNA Fendrr in vitro, which will provide a novel insight into the therapeutic target for AP.
BackgroundThe diagnosis of associated choledocholithiasis prior to cholecystectomy for patients with gallstones is important for the surgical decision and treatment efficacy. However, whether ultrasound is sufficient for preoperative diagnosis of choledocholithiasis remains controversial, with different opinions on whether routine magnetic resonance cholangiopancreatography (MRCP) is needed to detect the possible presence of common bile duct (CBD) stones.MethodsIn this study, a total of 413 patients with gallstones who were admitted to the Department of General Surgery of the First Affiliated Hospital of Harbin Medical University in China for a period of 3 years and underwent both ultrasound and MRCP examinations were retrospectively analysed. After reviewing and screening these cases according to the literature, 11 indicators including gender, age, alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, indirect bilirubin, alkaline phosphatase, γ-aminotransferase, CBD diameter, and concurrent acute cholecystitis were selected and comparatively analysed.ResultsAmong the 413 patients, a total of 109 cases showed concurrent gallstones and choledocholithiasis, accounting for 26.39 % of all cases. Among them, 60 cases of choledocholithiasis were revealed by ultrasound examination, accounting for 55.05 %, while 49 cases of choledocholithiasis were not detected by ultrasound examination but were confirmed by MRCP instead (the missed diagnosis rate of ultrasound was 44.95 %). The results of statistical analysis suggested that alanine aminotransferase, acute cholecystitis, and CBD diameter were the three most relevant factors for missed diagnosis by ultrasound.ConclusionThe accuracy of preoperative ultrasonography for the diagnosis of associated CBD stones for patients with gallstones is not high. However, elevated alanine aminotransferase, concurrent acute cholecystitis, and CBD diameter were identified as key factors that may affect the accuracy of the diagnosis. Thus, routine preoperative MRCP examination is suggested for patients with gallstones to rule out possible concomitant CBD stones.
In recent years, an increasing number of studies on the roles of macrophages in tumors, immune responses and metabolism have been published, in which macrophage polarization has been an extensively discussed topic. In the present study, differentially expressed genes in various types of macrophages were analyzed using the Gene Expression Omnibus database. Cluster analysis of differentially expressed genes was conducted, and a protein-protein interaction (PPI) network was constructed. Finally, modular analysis and functional enrichment analysis revealed that a Toll-like receptor (TLR) signaling pathway is involved in the regulation of macrophage polarization. Furthermore, the high-degree proteins in the PPI network that are involved in the molecular regulation of macrophage polarization are closely associated with proteins of the TLR signaling pathway. These results suggested that the TLR signaling pathways may be a principal direction of future research on the regulation of macrophage polarization.
This study was performed to screen miRNAs and mRNAs that are differentially expressed during trypsinogen activation in acute pancreatitis and to verify their role in the process of trypsinogen activation. The function enrichment analysis showed that the functions of miR-352 and its regulatory targets lysosome-associated membrane protein 2 (LAMP2) and cathepsin L1 (CTSL1) were lysosome related. The results of the verification experiment showed that in the TLC-S-treated AR42J (pancreatic cell line) cells, miR-352 expression increased, expression levels of LAMP2 and CTSL1 were significantly reduced, trypsinogen activation was increased, and the autophagy pathway was blocked. In the miR-352 mimic-transfected cells, miR-352 expression increased, expression levels of LAMP2 and CTSL1 were significantly reduced, trypsinogen activation was increased, intracellular lysosomal pH increased, cathepsins L activity decreased and the amount of autophagolysosomes increased. In the miR-352 inhibitor-transfected cells, miR-352 expression was reduced, expression levels of LAMP2 and CTSL1 were significantly increased, trypsinogen activation was decreased, intracellular lysosomal pH decreased, cathepsins L activity increased and the amount of autophagolysosomes decreased. In the process of taurolithocholic acid 3-sulfate (TLC-S) induced trypsinogen activation, overexpression of miR-352 could down-regulate LAMP2 and CTSL1, resulting in the dysfunction of autophagic lysosome. Thus, the autophagy pathway was blocked, and trypsinogen activation was enhanced.
This study aims to determine the differentially expressed proteins in the pancreatic acinar cells undergoing apoptosis and oncosis stimulated with caerulein to explore different cell death process of the acinar cell. AR42J cells were treated with caerulein to induce cell model of acute pancreatitis. Cells that were undergoing apoptosis and oncosis were separated by flow cytometry. Then differentially expressed proteins in the two groups of separated cells were detected by shotgun liquid chromatography-tandem mass spectrometry. The results showed that 11 proteins were detected in both apoptosis group and oncosis group, 17 proteins were detected only in apoptosis group and 29 proteins were detected only in oncosis group. KEGG analysis showed that proteins detected only in apoptosis group were significantly enriched in 10 pathways, including ECM-receptor interaction, cell adhesion molecules, and proteins detected only in oncosis group were significantly enriched in three pathways, including endocytosis, base excision repair, and RNA degradation. These proteins we detected are helpful for us to understand the process of cell death in acute pancreatitis and may be useful for changing the death mode of pancreatic acinar cells, thus attenuating the severity of pancreatitis.
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