Muscle Tissue Exosome Research and Application

Exosomes can be secreted by muscle tissue cells, including various types of muscle cells (e.g. cardiac, skeletal, and smooth muscle) as well as muscle-associated cells (e.g. vascular endothelial cells and red blood cells). Past research has shown that muscle tissue-derived exosomes are biologically important in many ways and are a key component in maintaining normal organismal physiological function. Creative Biolabs offers muscle tissue exosome-related research and applications to help understand the potential functions and mechanisms. Muscle tissue exosomes function by releasing biologically active molecules such as miRNAs and proteins that affect the physiological state of the recipient cells and remodel the extracellular matrix. Various functions and mechanisms have been investigated for muscle tissue exosomes.

Regulating Metabolic Processes

The beneficial metabolic effects of exercise are mediated, at least in part, by releasing soluble factors from muscle, with exosomes being small vesicles that facilitate the exchange of biological components between cells and tissues possibly involved in muscle regulation of metabolic processes. Exosomes isolated from trained mouse muscle underwent altered miRNA profiles compared to normal mice, including a significant increase in miR-133a and miR-133b. Importantly, it exhibited improved glucose tolerance. This mainly resulted from the altered miRNA targeting down-regulation of insulin-regulated transcription FoxO1 (factor forkhead box O1) expression in the liver. Also, treatment of exosomes with exogenous transfected miR-133b mimics and FoxO1-specific siRNA confirmed the altered metabolic effects of this signaling pathway in mice. These data demonstrate the impact of exercise on the miRNA profile of muscle tissue exosomes, which improves the organism's metabolic profile and prolongs survival.

Fig.1 Exercise alters the miRNA profile of muscle tissue exosomes. (Castaño, 2020)

Promotes Muscle Development, Osteogenic Differentiation, and Adipose Homeostasis

Muscle tissue exosomes also play a regulatory role in muscle, bone, and adipose tissue homeostasis. For example, during the development of myotubes to myoblasts, myotubular exosomes are more abundant in muscle contraction-associated proteins, including myotonic dystrophy protein-associated glycoprotein 1, lipoprotein Cy, and titin, compared to myoblast exosomes. This targets the down-regulation of Cyclin-D1 and up-regulation of Myogenin protein expression to inhibit myoblast proliferation and promote their differentiation. Meanwhile, skeletal muscle exosomes regulate muscle development by secreting insulin growth factor and platelet growth factor AA. In addition, muscle also achieves mutual regulation with bone by means of muscle tissue exosomes in an endocrine manner. By miRNA-seq of exosomes and quantifying gene expression after osteogenic differentiation, myoblast-derived exosomes were screened to induce osteogenic differentiation by acting on osteoblasts and delivering the key molecule miR-27a-3p. Skeletal muscle exosomes were also shown to act on adipose and adipose stem cells to maintain homeostasis.

Fig.2 Role of skeletal muscle exosomes on adipose homeostasis. (Rome, 2022)

Muscle Tissue Repair and Regeneration

Muscle tissue-derived exosomes also have great therapeutic potential in the field of regenerative medicine as cell-free therapies for muscle injury. HGF (hepatocyte growth factor), a powerful catalyst for muscle stem cell activation and translocation to damaged sites, has been identified in exosomes from differentiating skeletal muscle cells, able to act in a dose-dependent manner in muscle repair and synergize with various myogenic factors such as FGF2, IGF1, and TGF-β. Meanwhile, exosomes released from muscle precursor cells contain miR-206, which promotes collagen synthesis in muscle fibroblasts and remodeling of the extracellular environment in muscle tissue by inhibiting Rrbp1 (ribosome binding protein 1).

Muscle Contraction Markers

Muscle tissue exosomes can likewise be studied as liquid biopsies and screening markers. Researchers explored the contents of human myometrial tissue exosomes, subjected them to quantitative liquid chromatography-tandem mass spectrometry and miRNA sequencing, and analyzed it in combination with a database, which revealed that GJA1 (gap junction protein) and SLC39A14 (solute carrier family 39 member 14) can be used as novel biomarkers for clinical detection of myometrial contraction.

Multifunctional muscle tissue exosomes have been shown to play a key role in regulating the onset and progression of a variety of diseases, such as cardiovascular disease, muscle atrophy, neurological disorders, etc. Creative Biolabs provides services for muscle tissue exosome research and applications to help explore their functions and mechanisms and deepen the understanding of their regulatory roles. Please contact us for more information.

References

Castaño, C.; et al. Delivery of muscle-derived exosomal miRNAs induced by HIIT improves insulin sensitivity through down-regulation of hepatic FoxO1 in mice. Proc Natl Acad Sci U S A. 2020, 117(48): 30335-30343.
Rome, S. Muscle and adipose tissue communicate with extracellular vesicles. Int J Mol Sci. 2022, 23(13): 7052.

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