AngII (angiotensin II) induces pathological conditions such as fibrosis in skeletal muscle. In this process, AngII increases ROS (reactive oxygen species) and induces a biphasic phosphorylation of p38 MAPK (mitogen-activated protein kinase). In addition, AngII stimulates the expression and production of TGF (transforming growth factor)-β1 via a mechanism dependent on ROS production mediated by NADPH oxidase (NOX) and p38 MAPK activation. In the present study, we investigated whether Ang-(1–7) [angiotensin-(1–7)], through the Mas-1 receptor, can counteract the signalling induced by AngII in mouse skeletal muscle and cause a decrease in the expression and further activity of TGF-β1 in skeletal muscle cells. Our results show that Ang-(1–7) decreased the expression of TGF-β1 induced by AngII in a dose-dependent manner. In addition, we observed that Ang-(1–7) prevented the increase in TGF-β1 expression induced by AngII, ROS production dependent on NOX and the early phase of p38 MAPK phosphorylation. Interestingly, Ang-(1–7) also prevented the late phase of p38 MAPK phosphorylation, Smad-2 phosphorylation and Smad-4 nuclear translocation, an increase in transcriptional activity, as determined using the p3TP-lux reporter, and fibronectin levels, all of which are dependent on the TGF-β1 levels induced by AngII. We also demonstrated that Ang-(1–7) prevented the increase in TGF-β1, fibronectin and collagen content in the diaphragm of mice infused with AngII. All of these effects were reversed by the administration of A779, indicating the participation of Mas-1. In conclusion, our findings support the hypothesis that Ang-(1–7) decreases the expression and further biological activity of TGF-β1 induced by AngII in vitro and in vivo.
Skip Nav Destination
Article navigation
Research Article|
April 16 2014
The Ang-(1–7)/Mas-1 axis attenuates the expression and signalling of TGF-β1 induced by AngII in mouse skeletal muscle
María Gabriela Morales;
María Gabriela Morales
*Laboratorio de Biología y Fisiopatología Molecular, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas & Facultad de Medicina, Universidad Andres Bello, Santiago, Chile
Search for other works by this author on:
Johanna Ábrigo;
Johanna Ábrigo
*Laboratorio de Biología y Fisiopatología Molecular, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas & Facultad de Medicina, Universidad Andres Bello, Santiago, Chile
Search for other works by this author on:
Carla Meneses;
Carla Meneses
*Laboratorio de Biología y Fisiopatología Molecular, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas & Facultad de Medicina, Universidad Andres Bello, Santiago, Chile
Search for other works by this author on:
Felipe Simon;
Felipe Simon
*Laboratorio de Biología y Fisiopatología Molecular, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas & Facultad de Medicina, Universidad Andres Bello, Santiago, Chile
†Instituto Milenio en Inmunología e Inmunoterapia, Santiago, Chile
Search for other works by this author on:
Franco Cisternas;
Franco Cisternas
*Laboratorio de Biología y Fisiopatología Molecular, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas & Facultad de Medicina, Universidad Andres Bello, Santiago, Chile
Search for other works by this author on:
Juan Carlos Rivera;
Juan Carlos Rivera
*Laboratorio de Biología y Fisiopatología Molecular, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas & Facultad de Medicina, Universidad Andres Bello, Santiago, Chile
Search for other works by this author on:
Yaneisi Vazquez;
Yaneisi Vazquez
*Laboratorio de Biología y Fisiopatología Molecular, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas & Facultad de Medicina, Universidad Andres Bello, Santiago, Chile
Search for other works by this author on:
Claudio Cabello-Verrugio
*Laboratorio de Biología y Fisiopatología Molecular, Departamento de Ciencias Biológicas, Facultad de Ciencias Biológicas & Facultad de Medicina, Universidad Andres Bello, Santiago, Chile
Correspondence: Dr Claudio Cabello-Verrugio (email [email protected]).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
September 17 2013
Revision Received:
February 03 2014
Accepted:
March 03 2014
Accepted Manuscript online:
March 03 2014
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2014 Biochemical Society
2014
Clin Sci (Lond) (2014) 127 (4): 251–264.
Article history
Received:
September 17 2013
Revision Received:
February 03 2014
Accepted:
March 03 2014
Accepted Manuscript online:
March 03 2014
Citation
María Gabriela Morales, Johanna Ábrigo, Carla Meneses, Felipe Simon, Franco Cisternas, Juan Carlos Rivera, Yaneisi Vazquez, Claudio Cabello-Verrugio; The Ang-(1–7)/Mas-1 axis attenuates the expression and signalling of TGF-β1 induced by AngII in mouse skeletal muscle. Clin Sci (Lond) 1 July 2014; 127 (4): 251–264. doi: https://doi.org/10.1042/CS20130585
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() |