RRC ID 45501
Author Baden MY, Fukui K, Hosokawa Y, Iwahashi H, Imagawa A, Shimomura I.
Title Examination of a Viral Infection Mimetic Model in Human iPS Cell-Derived Insulin-Producing Cells and the Anti-Apoptotic Effect of GLP-1 Analogue.
Journal PLoS One
Abstract AIMS:Viral infection is associated with pancreatic beta cell destruction in fulminant type 1 diabetes mellitus. The aim of this study was to investigate the acceleration and protective mechanisms of beta cell destruction by establishing a model of viral infection in pancreatic beta cells.
METHODS:Polyinosinic:polycytidylic acid was transfected into MIN6 cells and insulin-producing cells differentiated from human induced pluripotent stem cells via small molecule applications. Gene expression was analyzed by real-time PCR, and apoptosis was evaluated by caspase-3 activity and TUNEL staining. The anti-apoptotic effect of Exendin-4 was also evaluated.
RESULTS:Polyinosinic:polycytidylic acid transfection led to elevated expression of the genes encoding IFNα, IFNβ, CXCL10, Fas, viral receptors, and IFN-inducible antiviral effectors in MIN6 cells. Exendin-4 treatment suppressed the elevated gene expression levels and reduced polyinosinic:polycytidylic acid-induced apoptosis both in MIN6 cells and in insulin-producing cells from human induced pluripotent stem cells. Glucagon-like peptide-1 receptor, protein kinase A, and phosphatidylinositol-3 kinase inhibitors counteracted the anti-apoptotic effect of Exendin-4.
CONCLUSIONS:Polyinosinic:polycytidylic acid transfection can mimic viral infection, and Exendin-4 exerted an anti-apoptotic effect both in MIN6 and insulin-producing cells from human induced pluripotent stem cells.
Volume 10(12)
Pages e0144606
Published 2015-1-1
DOI 10.1371/journal.pone.0144606
PII PONE-D-15-36470
PMID 26659307
PMC PMC4676675
MeSH Antiviral Agents / pharmacology Apoptosis / drug effects Cell Differentiation Cells, Cultured Chemokine CXCL10 / genetics Chemokine CXCL10 / metabolism Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors Cyclic AMP-Dependent Protein Kinases / genetics Cyclic AMP-Dependent Protein Kinases / metabolism Enzyme Inhibitors / pharmacology Exenatide Gene Expression Regulation Glucagon-Like Peptide-1 Receptor / antagonists & inhibitors Glucagon-Like Peptide-1 Receptor / genetics Glucagon-Like Peptide-1 Receptor / metabolism Humans Hypoglycemic Agents / pharmacology* Induced Pluripotent Stem Cells / drug effects Induced Pluripotent Stem Cells / metabolism* Induced Pluripotent Stem Cells / pathology Insulin-Secreting Cells / drug effects Insulin-Secreting Cells / metabolism* Insulin-Secreting Cells / pathology Interferon Inducers / pharmacology Interferon-alpha / genetics Interferon-alpha / metabolism Interferon-beta / genetics Interferon-beta / metabolism Models, Biological* Peptides / pharmacology* Phosphatidylinositol 3-Kinases / genetics Phosphatidylinositol 3-Kinases / metabolism Phosphoinositide-3 Kinase Inhibitors Poly I-C / genetics Poly I-C / pharmacology Receptors, Virus / genetics Receptors, Virus / metabolism Signal Transduction Transfection Venoms / pharmacology* Virus Diseases / genetics Virus Diseases / metabolism Virus Diseases / pathology fas Receptor / genetics fas Receptor / metabolism
IF 2.74
Times Cited 1
Human and Animal Cells 409B2(HPS0076)