SiRNA-mediated PIAS1 silencing promotes inflammatory response and leads to injury of cerulein-stimulated pancreatic acinar cells via regulation of the P38MAPK signaling pathway
Our aim in this study was to investigate the changes of inflammatory response by protein inhibitor of activated signal transducer and activator of transcription 1 (PIAS1) gene silencing treatment in cerulein-stimulated AR42J cells, and relate them to changes in cell injury, thus providing evidence for developing clinical therapies. This study examined the effects of cerulein on the activity of P38 mitogen activated protein kinase (P38MAPK), c-jun NH2-terminal kinase/stress-activated protein kinase and the inflammatory mediators released by PIAS1 gene-silenced AR42J cells. Consequently, the markers including DNA ladder, cell apoptotic rat, cell cycles, levels of cell cycle and apoptotic related factors were used to determine the effects of PIAS1 gene silencing on the cerulein-induced cell injury. The results indicated that in the cerulein-stimulated PIASI silencing cells, the activity of P38MAPK was enhanced, while at the same time, the levels of inflammatory mediators such as the tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and matrix metallopeptidase-9, were markedly higher than those of other cerulein-stimulated cells. Thus, the cerulein-stimulated PIASI gene-silenced cells obviously increased cell arrest in the G1/M phase by increasing P21 and P27 expression, and also induced apoptosis by regulating the P53 signaling pathway. This study suggests that the down-regulation of PIAS1 is efficacious at enhancing the expression of inflammatory mediators and inducing cell injury in acute pancreatitis (AP), thus deteriorating the severity of disease. It provides evidence that PIAS1 is a potential therapeutic target for AP.
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Document Type: Research Article
Affiliations: Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
Publication date: October 1, 2010
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- The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.
The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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