Skeletal muscle regeneration in mice is stimulated by local overexpression of V1a-vasopressin receptor Skeletal muscle has a remarkable capacity to regenerate after mechanical or pathological injury. We show that the V1a receptor (V1aR) for vasopressin, a potent myogenic-promoting factor that stimulates differentiation and hypertrophy in vitro, is expressed in mouse skeletal muscle and modulated during regeneration after experimental injury. We used gene delivery by electroporation to overexpress the myc-tagged vasopressin V1aR in specific muscles, thus sensitizing them to circulating vasopressin. The correct localization on the surface of the fibers of the recombinant product was demonstrated by confocal immunofluorescence directed against the myc tag. V1aR overexpression dramatically enhanced regeneration. When compared with mock-transfected controls, V1aR overexpressing muscles exhibited significantly accelerated activation of satellite cells and increased expression of differentiation markers. Downstream of V1aR activation, calcineurin was strongly up-regulated and stimulated the expression of IL-4, a potent mediator of myogenic cell fusion. The central role of calcineurin in mediating V1aR-dependent myogenesis was also demonstrated by using its specific inhibitor, cyclosporine A. This study identifies skeletal muscle as a physiological target of hormones of the vasopressin family and reveals a novel in vivo role for vasopressin-dependent pathways. These findings unveil several steps, along a complex signaling pathway, that may be exploited as potential targets for the therapy of diseases characterized by altered muscle homeostasis and regeneration.

La rigenerazione del muscolo scheletrico nei topi è stimolata dalla iperespressione locale del recettore V1a della vasopressina / Toschi, Angelica; Severi, ANNA LISA; Coletti, Dario; Catizone, Angiolina; Musaro', Antonio; Molinaro, Mario; Nervi, Clara; Adamo, Sergio; Scicchitano, B. M.; Centanni, Marco; Cellini, Miriam. - In: L'ENDOCRINOLOGO. - ISSN 1590-170X. - ELETTRONICO. - (2011), pp. 309-309. [10.1007/BF03344861]

La rigenerazione del muscolo scheletrico nei topi è stimolata dalla iperespressione locale del recettore V1a della vasopressina

TOSCHI, ANGELICA;SEVERI, ANNA LISA;COLETTI, Dario;CATIZONE, Angiolina;MUSARO', Antonio;MOLINARO, Mario;NERVI, Clara;ADAMO, Sergio;CENTANNI, Marco;CELLINI, MIRIAM
2011

Abstract

Skeletal muscle regeneration in mice is stimulated by local overexpression of V1a-vasopressin receptor Skeletal muscle has a remarkable capacity to regenerate after mechanical or pathological injury. We show that the V1a receptor (V1aR) for vasopressin, a potent myogenic-promoting factor that stimulates differentiation and hypertrophy in vitro, is expressed in mouse skeletal muscle and modulated during regeneration after experimental injury. We used gene delivery by electroporation to overexpress the myc-tagged vasopressin V1aR in specific muscles, thus sensitizing them to circulating vasopressin. The correct localization on the surface of the fibers of the recombinant product was demonstrated by confocal immunofluorescence directed against the myc tag. V1aR overexpression dramatically enhanced regeneration. When compared with mock-transfected controls, V1aR overexpressing muscles exhibited significantly accelerated activation of satellite cells and increased expression of differentiation markers. Downstream of V1aR activation, calcineurin was strongly up-regulated and stimulated the expression of IL-4, a potent mediator of myogenic cell fusion. The central role of calcineurin in mediating V1aR-dependent myogenesis was also demonstrated by using its specific inhibitor, cyclosporine A. This study identifies skeletal muscle as a physiological target of hormones of the vasopressin family and reveals a novel in vivo role for vasopressin-dependent pathways. These findings unveil several steps, along a complex signaling pathway, that may be exploited as potential targets for the therapy of diseases characterized by altered muscle homeostasis and regeneration.
2011
Vasopressin, V1a receptor, skeletal muscle, transcription, Mef2
01 Pubblicazione su rivista::01a Articolo in rivista
La rigenerazione del muscolo scheletrico nei topi è stimolata dalla iperespressione locale del recettore V1a della vasopressina / Toschi, Angelica; Severi, ANNA LISA; Coletti, Dario; Catizone, Angiolina; Musaro', Antonio; Molinaro, Mario; Nervi, Clara; Adamo, Sergio; Scicchitano, B. M.; Centanni, Marco; Cellini, Miriam. - In: L'ENDOCRINOLOGO. - ISSN 1590-170X. - ELETTRONICO. - (2011), pp. 309-309. [10.1007/BF03344861]
File allegati a questo prodotto
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/878507
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact