title: Pancreatic Acinar Cells Employ miRNAs as Mediators of Intercellular Communication to Participate in the Regulation of Pancreatitis-Associated Macrophage Activation.
abstract: Macrophage activation plays an important role in the inflammatory response in acute pancreatitis. In the present study, the activation of AR42J pancreatic acinar cells was induced by taurolithocholate treatment. The results showed that the culture medium from the activated AR42J cells significantly enhanced NFκB activation in the macrophages compared to that without taurolithocholate treatment. Additionally, the precipitates obtained from ultracentrifugation of the culture media that were rich in exosomes were markedly more potent in activating macrophages compared with the supernatant fraction lacking exosomes. The results indicated that the mediators carried by the exosomes played important roles in macrophage activation. Exosomal miRNAs were extracted and examined using microarrays. A total of 115 differentially expressed miRNAs were identified, and 30 showed upregulated expression, while 85 displayed downregulated expression. Target genes of the differentially expressed miRNAs were predicted using TargetScan, MiRanda, and PicTar software programs. The putative target genes were subjected to KEGG functional analysis. The functions of the target genes were primarily enriched in MAPK pathways. Specifically, the target genes regulated macrophage activation through the TRAF6-TAB2-TAK1-NIK/IKK-NFκB pathway. As the mediators of signal transduction, miRNAs and their predicted target mRNAs regulate every step in the MAPK pathway.
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90064, USA.
authors.forename: Ming
authors.identifier: 0000-0003-1574-9850
authors.initials: M
authors.lastname: Lu
authors.affiliation: Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90064, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Qiao
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China.
authors.forename: Weihui
authors.identifier: 0000-0002-3180-3004
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China.
authors.forename: Dongbo
authors.identifier: 0000-0002-2675-8472
authors.initials: D
authors.lastname: Xue
mesh_terms: D061354:Acinar Cells / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D024202:Electrophoretic Mobility Shift Assay; D063326:Exosome Multienzyme Ribonuclease Complex / Q000235:genetics; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010179:Pancreas / Q000166:cytology*; D010195:Pancreatitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014362:Trypsinogen / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D016328:NF-kappa B; D014362:Trypsinogen; D063326:Exosome Multienzyme Ribonuclease Complex