ACE2 Is Augmented in Dystrophic Skeletal Muscle and Plays a Role in Decreasing Associated Fibrosis

Riquelme, Cecilia; Acuña, María José; Torrejón, Javiera; Rebolledo, Daniela L.; Cabrera, Daniel; Santos, Robson A.S.; Brandan, Enrique

doi:10.1371/journal.pone.0093449

Cited by 53 publications

(57 citation statements)

References 53 publications

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“…Ang (1-7), mainly produced from Ang II by ACE2 and signaling through the Mas receptor, has been reported to regulate skeletal muscle insulin sensitivity (34,35), decrease fibrosis, and improve muscle function in a mouse model of muscle dystrophy (36). It has been shown by us (2-9) and by others (10 -12) (4,18), which is consistent with the fact that adult muscle fibers express little to no Ang II receptors (18,19).…”

Section: Discussionsupporting

confidence: 72%

Angiotensin Type 2 Receptor Signaling in Satellite Cells Potentiates Skeletal Muscle Regeneration

Yoshida

Huq

Delafontaine

2014

Journal of Biological Chemistry

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Background: Angiotensin II induces skeletal muscle atrophy, but the function of other renin-angiotensin system components in skeletal muscle physiology is understood poorly. Results: Angiotensin II type 2 receptor (AT2R) blockade inhibits skeletal muscle regeneration and myoblast differentiation. Conclusion: AT2R positively regulates skeletal muscle regeneration. Significance: Stimulation of AT2R signaling may be beneficial in muscle wasting conditions.

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Section: Discussionsupporting

confidence: 72%

Angiotensin Type 2 Receptor Signaling in Satellite Cells Potentiates Skeletal Muscle Regeneration

Yoshida

Huq

Delafontaine

2014

Journal of Biological Chemistry

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“…Few studies have demonstrated that non-classical RAS axis is active in skeletal muscle [26,37,48,49]. Our study showed that Ang-(1-7) recovers muscle strength that was reduced by LPS.…”

Section: Discussionsupporting

confidence: 52%

Endotoxin-induced skeletal muscle wasting is prevented by angiotensin-(1–7) through a p38 MAPK-dependent mechanism

et al. 2015

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Skeletal muscle atrophy induced during sepsis syndrome produced by endotoxin in the form of LPS (lipopolysaccharide), is a pathological condition characterized by the loss of strength and muscle mass, an increase in MHC (myosin heavy chain) degradation, and an increase in the expression of atrogin-1 and MuRF-1 (muscle-specific RING-finger protein 1), two ubiquitin E3 ligases belonging to the ubiquitin-proteasome system. Ang-(1-7) [Angiotensin-(1-7)], through its Mas receptor, has beneficial effects in skeletal muscle. We evaluated in vivo the role of Ang-(1-7) and Mas receptor on the muscle wasting induced by LPS injection into C57BL/10J mice. In vitro studies were performed in murine C2C12 myotubes and isolated myofibres from EDL (extensor digitorum longus) muscle. In addition, the participation of p38 MAPK (mitogen-activated protein kinase) in the Ang-(1-7) effect on the LPS-induced muscle atrophy was evaluated. Our results show that Ang-(1-7) prevents the decrease in the diameter of myofibres and myotubes, the decrease in muscle strength, the diminution in MHC levels and the induction of atrogin-1 and MuRF-1 expression, all of which are induced by LPS. These effects were reversed by using A779, a Mas antagonist. Ang-(1-7) exerts these anti-atrophic effects at least in part by inhibiting the LPS-dependent activation of p38 MAPK both in vitro and in vivo. We have demonstrated for the first time that Ang-(1-7) counteracts the skeletal muscle atrophy induced by endotoxin through a mechanism dependent on the Mas receptor that involves a decrease in p38 MAPK phosphorylation. The present study indicates that Ang-(1-7) is a novel molecule with a potential therapeutic use to improve muscle wasting during endotoxin-induced sepsis syndrome.

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“…Fibre diameter was detected by using wheat germ agglutinin (WGA) staining, which labels glycoproteins at the sarcolemma [44,45]. Briefly, freshly frozen gastrocnemius muscles were sectioned and cryosections (7 μm) were placed on glass slides, fixed in 4 % paraformaldehyde followed by incubation with AlexaFluor ® -594-conjugated WGA (Molecular Probes).…”

Section: Fibre Diameter Determination and Quantificationmentioning

confidence: 99%

Angiotensin-(1–7) decreases skeletal muscle atrophy induced by angiotensin II through a Mas receptor-dependent mechanism

et al. 2014

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Skeletal muscle atrophy is a pathological condition characterized by the loss of strength and muscle mass, an increase in myosin heavy chain (MHC) degradation and increase in the expression of two muscle-specific ubiquitin ligases: atrogin-1 and MuRF-1. Angiotensin II (AngII) induces muscle atrophy. Angiotensin-(1-7) [Ang-(1-7)], through its receptor Mas, produces the opposite effects than AngII. We assessed the effects of Ang-(1-7) on the skeletal muscle atrophy induced by AngII. Our results show that Ang-(1-7), through Mas, prevents the effects induced by AngII in muscle gastrocnemius: the decrease in the fibre diameter, muscle strength and MHC levels and the increase in atrogin-1 and MuRF-1. Ang-(1-7) also induces AKT phosphorylation. In addition, our analysis in vitro using C2C12 myotubes shows that Ang-(1-7), through a mechanism dependent on Mas, prevents the decrease in the levels of MHC and the increase in the expression of the atrogin-1 and MuRF-1, both induced by AngII. Ang-(1-7) induces AKT phosphorylation in myotubes; additionally, we demonstrated that the inhibition of AKT with MK-2206 decreases the anti-atrophic effects of Ang-(1-7). Thus, we demonstrate for the first time that Ang-(1-7) counteracts the skeletal muscle atrophy induced by AngII through a mechanism dependent on the Mas receptor, which involves AKT activity. Our study indicates that Ang-(1-7) is novel molecule with a potential therapeutical use to improve muscle wasting associated, at least, with pathologies that present high levels of AngII.

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ACE2 Is Augmented in Dystrophic Skeletal Muscle and Plays a Role in Decreasing Associated Fibrosis

Cited by 53 publications

References 53 publications

Angiotensin Type 2 Receptor Signaling in Satellite Cells Potentiates Skeletal Muscle Regeneration

Angiotensin Type 2 Receptor Signaling in Satellite Cells Potentiates Skeletal Muscle Regeneration

Endotoxin-induced skeletal muscle wasting is prevented by angiotensin-(1–7) through a p38 MAPK-dependent mechanism

Angiotensin-(1–7) decreases skeletal muscle atrophy induced by angiotensin II through a Mas receptor-dependent mechanism

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