Effects of Egr1 on pancreatic acinar intracellular trypsinogen activation and the associated ceRNA network

Abstract

acute pancreatitis (aP) is a common digestive disorder with high morbidity and mortality. The present study aimed to investigate the expression of early growth response protein 1 (egr1), and the effect of competing endogenous (ce)rna network on trypsinogen activation. Pancreatic acinar intracellular trypsinogen activation (PaiTa) is an important event in the early stage of aP; however, the underlying mechanisms remain unclear. The present study used taurolithocholic acid 3-sulfate (Tlc-S)-treated ar42J cells (pancreatic cell line) to establish a PaiTa model. a gene microarray and bioinformatics analysis was performed to identify the potential key targets in PaiTa. The results demonstrated that egr1, an important transcription factor, was significantly overexpressed in PAITA. In Egr1 small interfering (si)rna-transfected cells, egr1 expression was decreased and trypsinogen activation was significantly decreased compared with negative control sirna-transfected cells, indicating that in Tlc-S-induced PaiTa, overexpression of egr1 enhanced trypsinogen activation. a cerna network [mrna-microrna (mirna/mir)-long non-coding (lnc)rna] generated using the PaiTa model revealed that the effects of egr1 on PaiTa may be regulated by multiple cerna pairs, and the lncrnas (including nonraTT022624 and nonraTT031002) and mirnas [including Rattus norvegicus (rno)-mir-214-3p and rno-mir-764-5p] included in the cerna pairs may serve roles in PaiTa by regulating the expression of egr1. The results of the present study may provide novel targets for researching the underlying mechanisms of, and developing treatments for aP.

Inflammation and Acinar Cell Dual-Targeting Nanomedicines for Synergistic Treatment of Acute Pancreatitis via Ca2+ Homeostasis Regulation and Pancreas Autodigestion Inhibition

“…PACs were treated with TLCS (100 nM) for 2 h to induce acinar cell injury . Following that, the cells were treated with free BA (200 ng mL –1 ), free Ga (0.75 μg mL –1 ), HMPB, HMPB@BA, HMPB@Ga, HMPB@BA#Ga, M@HMPB@BA#Ga, and 2N@M@HMPB@BA#Ga NPs for 12 h, while the control group was treated with an equal volume of PBS.…”

“…PACs were treated with TLCS (100 nM) for 2 h to induce acinar cell injury. 66 Following that, the cells were treated with free BA (200 ng mL −1 ), free Ga (0.75 μg mL −1 ), HMPB, HMPB@BA, HMPB@Ga, HMPB@BA#Ga, M@HMPB@BA#Ga, and 2N@M@ HMPB@BA#Ga NPs for 12 h, while the control group was treated with an equal volume of PBS. Subsequently, cells with different treatments were collected and centrifuged, and cell suspensions were collected for further flow cytometry analysis, whereas the supernatant was used as the conditioned medium for macrophages.…”

Role of lncRNAs in acute pancreatitis: pathogenesis, diagnosis, and therapy

“…These findings showed the important role of lncRNA TCONS_00021785 in protecting acinar cells by reducing zymogen activation. In another study, Gao B. et al (2020) found that lncRNA NONRATT022624 and NONRATT031002 could regulate the expression of early growth response protein 1 (Egr1, a transcription factor) by binding miR-214-3p and miR-764-5p, resulting in increased trypsinogen activation. These studies suggested that lncRNAs may play a key role in trypsinogen activation.…”

Mechanism of Magnolia Volatile Oil in the Treatment of Acute Pancreatitis Based on GC‐MS, Network Pharmacology, and Molecular Docking

“…Acute pancreatitis (AP) is the most frequent digestive system illness with both high morbidity and mortality [1,2]. Te overall incidence rate of AP is 4.8-38 per 100,000 annually [3][4][5][6] and continually increasing [7,8].…”