Angiotensin 1-7 Improves Skeletal Muscle Regeneration
Researchers here demonstrate that administration of angiotensin (1-7) protein to injured muscles in mice provokes improved regeneration of muscle tissue. Protein therapies are an expensive proposition at this point in time, so the usual approach for research of this nature is to look for a small molecule that upregulates expression of the desired protein. That said, gene therapies are looking ever more promising for any use case in which the objective is to increase levels of a circulating protein. Only a small number of cells, such as subcutaneous fat cells, need to be transfected via an injected therapy in order to produce a factory to generate that protein. That is a feasible goal if using presently available, well-established gene therapy technologies.
Skeletal muscle possesses regenerative potential via satellite cells, compromised in muscular dystrophies leading to fibrosis and fat infiltration. Angiotensin II (Ang-II) is commonly associated with pathological states. In contrast, Angiotensin (1-7) [Ang-(1-7)] counters Ang-II, acting via the Mas receptor. While Ang-II affects skeletal muscle regeneration, the influence of Ang-(1-7) remains to be elucidated. Therefore, this study aims to investigate the role of Ang-(1-7) in skeletal muscle regeneration.
C2C12 muscle cells were differentiated in the absence or presence of 10 nM of Ang-(1-7). The diameter of myotubes and protein levels of myogenin and myosin heavy chain (MHC) were determined. C57BL/6 wild-type male mice (16-18 weeks old) were randomly assigned to injury-vehicle, injury-Ang-(1-7), and control groups. Ang-(1-7) was administered via osmotic pumps, and muscle injury was induced by injecting barium chloride to assess muscle regeneration through histological analyses. Moreover, embryonic myosin (eMHC) and myogenin protein levels were evaluated.
C2C12 myotubes incubated with Ang-(1-7) showed larger diameters than the untreated group and increased myogenin and MHC protein levels during differentiation. Ang-(1-7) administration enhances regeneration by promoting a larger diameter of new muscle fibers. Furthermore, higher numbers of eMHC (+) fibers were observed in the injured-Ang-(1-7), which also had a larger diameter. Moreover, eMHC and myogenin protein levels were elevated, supporting enhanced regeneration due to Ang-(1-7) administration. Ang-(1-7) effectively promotes differentiation in vitro and improves muscle regeneration in the context of injuries, with potential implications for treating muscle-related disorders.