IBBEA   24401
INSTITUTO DE BIODIVERSIDAD Y BIOLOGIA EXPERIMENTAL Y APLICADA
Unidad Ejecutora - UE
artículos
Título:
Injury-induced purinergic signalling molecules upregulate pluripotency gene expression and mitotic activity of progenitor cells in the zebrafish retina
Autor/es:
BERNABEU RO; BEJARANO CA; BERNABEU RO; BEJARANO CA; VENERA GD; MEDRANO MP; VENERA GD; MEDRANO MP; FAILLACE MP; BATTISTA AG; FAILLACE MP; BATTISTA AG
Revista:
PURINERGIC SIGNALLING
Editorial:
SPRINGER
Referencias:
Año: 2017 p. 443 - 465
ISSN:
1573-9538
Resumen:
ABSTRACT<br />Damage in fish activates retina repair that restores sight. The purinergic signalling system serves multiple<br />homeostatic functions and has been implicated in cell cycle control of progenitor cells in the developing<br />retina. We examined whether changes in the expression of purinergic molecules were instrumental in the<br />proliferative phase after injury of adult zebrafish retinas with ouabain. P2RY1 mRNA increased early after<br />injury and showed maximal levels at the time of peak progenitor cell proliferation. Extracellular<br />nucleotides, mainly ADP, regulate P2RY1 transcriptional and protein expression. The injury-induced<br />upregulation of P2RY1 is mediated by an autoregulated mechanism. After injury, the transcriptional<br />expression of ecto-nucleotidases and ecto-ATPases also increased and ecto-ATPase activity inhibitors<br />decreased Müller glia-derived progenitor cell amplification. Inhibition of P2RY1 endogenous activation<br />prevented progenitor cell proliferation at two intervals after injury: one in which progenitor Müller glia<br />mitotically activates and a second one in which Müller glia-derived progenitor cells amplify. ADPS<br />induced the expression of lin28a and ascl1a genes in mature regions of uninjured retinas. The expression<br />of these genes, which regulate multipotent Müller glia reprogramming, was significantly inhibited by<br />blocking the endogenous activation of P2RY1 early after injury. We consistently observed that the number<br />of GFAP-BrdU-positive Müller cells after injury was larger in the absence than in the presence of the<br />P2RY1 antagonist. Ecto-ATPase activity inhibitors or P2RY1 specific antagonists did not modify apoptotic<br />cell death at the time of peak progenitor cell proliferation. The results suggested that ouabain injury<br />upregulates specific purinergic signals which stimulates multipotent progenitor cell response.