Blockade of Bradykinin receptors worsens the dystrophic phenotype of mdx mice: differential effects for B1 and B2 receptors

María José Acuña, Daniela Salas, Adriana Córdova-Casanova, Meilyn Cruz-Soca, Carlos Céspedes, Carlos P. Vio*, Enrique Brandan

*Autor correspondiente de este trabajo

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

17 Citas (Scopus)

Resumen

The Kallikrein Kinin System (KKS) is a vasoactive peptide system with known functions in the maintenance of tissue homeostasis, renal function and blood pressure. The main effector peptide of KKS is Bradykinin (BK). This ligand has two receptors: a constitutive B2 receptor (B2R), which has been suggested to have anti-fibrotic effects in renal and cardiac models of fibrosis; and the inducible B1 receptor (B1R), whose expression is induced by damage and inflammation. Inflammation and fibrosis are hallmarks of Duchenne muscular dystrophy (DMD), therefore we hypothesized that the KKS may play a role in this disease. To evaluate this hypothesis we used the mdx mouse a model for DMD. We blocked the endogenous activity of the KKS by treating mdx mice with B2R antagonist (HOE-140) or B1R antagonist (DesArgLeu8BK (DALBK)) for four weeks. Both antagonists increased damage, fibrosis, TGF-β and Smad-dependent signaling, CTGF/CCN-2 levels as well as the number of CD68 positive inflammatory cells. B2R blockade also reduced isolated muscle contraction force. These results indicate that the endogenous KKS has a protective role in the dystrophic muscle. The KKS may be a new target for future therapies to reduce inflammation and fibrosis in dystrophic muscle.

Idioma originalInglés
Páginas (desde-hasta)589-601
Número de páginas13
PublicaciónJournal of Cell Communication and Signaling
Volumen12
N.º3
DOI
EstadoPublicada - 2018
Publicado de forma externa

Nota bibliográfica

Publisher Copyright:
© 2018, The International CCN Society.

Áreas temáticas de ASJC Scopus

  • Bioquímica
  • Biología molecular
  • Biología celular

Huella

Profundice en los temas de investigación de 'Blockade of Bradykinin receptors worsens the dystrophic phenotype of mdx mice: differential effects for B1 and B2 receptors'. En conjunto forman una huella única.

Citar esto