Cyclic AMP signaling restricts activation and promotes maturation and antioxidant defenses in astrocytes
Paco, Sònia (Universitat de Barcelona)
Hummel, Manuela (Centre de Regulació Genòmica)
Plá, Virginia (Universitat de Barcelona)
Sumoy, Lauro (Institut Germans Trias i Pujol. Institut de Medicina Predictiva i Personalitzada del Càncer)
Aguado, Fernando (Universitat de Barcelona)

Fecha:	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.
Ayudas:	Ministerio de Economía y Competitividad BFU2010-22132 Ministerio de Economía y Competitividad BFU2013-48822-R Agència de Gestió d'Ajuts Universitaris i de Recerca 2014/SGR-01178
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Antioxidant defense ; Astrocytes ; Brain ; Differentiation ; NR2C ; Reactive glia ; Transcriptomic ; Camp
Publicado en:	BMC genomics, Vol. 17, Núm. 304 (April 2016) , ISSN 1471-2164

DOI: 10.1186/s12864-016-2623-4
PMID: 27108081

11 p, 2.2 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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