Cyclic AMP signaling restricts activation and promotes maturation and antioxidant defenses in astrocytes
Por:
Paco-Mercader S, Hummel M, Plá V, Sumoy L and Aguado F
Publicada:
23 abr 2016
Ahead of Print:
23 abr 2016
Resumen:
Background: cAMP signaling produces dramatic changes in astrocyte morphology and physiology. However, its involvement in phenotype acquisition and the transcriptionally mediated mechanisms of action are largely unknown.
Results: Here we analyzed the global transcriptome of cultured astroglial cells incubated with activators of cAMP pathways. A bulk of astroglial transcripts, 6221 annotated genes, were differentially regulated by cAMP signaling. cAMP analogs strongly upregulated genes involved in typical functions of mature astrocytes, such as homeostatic control, metabolic and structural support to neurons, antioxidant defense and communication, whereas they downregulated a considerable number of proliferating and immaturity-related transcripts. Moreover, numerous genes typically activated in reactive cells, such as scar components and immunological mediators, were repressed by cAMP. GSEA analysis contrasting gene expression profiles with transcriptome signatures of acutely isolated astrocytes and in situ evaluation of protein levels in these cells showed that cAMP signaling conferred mature and in vivo-like transcriptional features to cultured astrocytes.
Conclusions: These results indicate that cAMP signaling is a key pathway promoting astrocyte maturation and restricting their developmental and activation features. Therefore, a positive modulation of cAMP signaling may promote the normal state of differentiated astrocytes and favor the protection and function of neuronal networks.
Filiaciones:
Paco-Mercader S:
Department of Cell Biology, University of Barcelona, Av. Diagonal 645, Barcelona, E-08028, Spain
Present address: Department of Pediatric Hematology and Oncology, Hospital Sant Joan de Déu Barcelona, Esplugues de Llobregat, E-08950, Spain
Hummel M:
Centre for Genomic Regulation, Barcelona, E-08003, Spain
Present address: Division of Biostatistics, German Cancer Research Center, Im Neuenheimer Feld 581, D-69120, Heidelberg, Germany
Plá V:
Department of Cell Biology, University of Barcelona, Av. Diagonal 645, Barcelona, E-08028, Spain
Institute of Neurosciences, University of Barcelona, Barcelona, E-08035, Spain
Sumoy L:
Institute for Predictive and Personalized Medicine of Cancer, Badalona, E-08916, Spain
Germans Trias i Pujol Health Sciences Research Institute, E-08916, Badalona, Spain
Aguado F:
Department of Cell Biology, University of Barcelona, Av. Diagonal 645, Barcelona, E-08028, Spain.
Institute of Neurosciences, University of Barcelona, Barcelona, E-08035, Spain.
Green Submitted, Green Published, gold
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