The secretome of skeletal muscle cells: A systematic review

Abstract

Background: Proteomic studies of the secretome of skeletal muscle cells can help us understand the processes that govern the synthesis, systemic interactions and organization of skeletal muscle and identify proteins that are involved in muscular adaptations to exercise, ageing and degeneration. In this systematic review, we aimed to summarize recent mass-spectrometry based proteomics discoveries on the secretome of skeletal muscle cells in response to disease, exercise or metabolic stress.

Methods: A literature search was performed in the Medline/Ovid and Scopus electronic bibliographic databases. Only papers reporting the analysis of the secretome by mass spectrometry were included.

Results: A total of 19 papers met the inclusion criteria for this systematic review. These papers included comparative analysis of differentially expressed proteins between healthy and unhealthy muscle cells and comparison of the secretome of skeletal muscle cells during myogenesis and after insulin stimulation or exercising. The proteins were separated into several categories and their differential secretion was compared. In total, 654 proteins were listed as being present in the secretome of muscle cells. Among them, 30 proteins were differentially regulated by physical exercise, 130 during myogenesis, 114 by dystrophin deficiency, 26 by muscle atrophy, 27 by insulin stimulation and finally 176 proteins secreted by insulin-resistant muscle cells.

Conclusions: This systematic review of the secretome of skeletal muscle cell in health and disease provides a comprehensive overview of the most regulated proteins in pathological or physiological conditions. These proteins might be therapeutic targets or biochemical markers of muscle diseases.

Keywords: Biomarkers; Mass spectrometry; Myokines; Proteomic; Secretome; Skeletal muscle cells.

Fig.1

Preferred reporting items for systematic reviews and meta-analysis (PRISMA) Flow diagram. No MS = No Mass Spectrometry.

Fig.2

The secretome analysis of skeletal muscle cells after exercising showed that no proteins were down-regulated and 30 proteins were up-regulated. Proteins were then classified and counted on the basis of their function.

Fig.3

The secretome analysis of skeletal muscle cells during myogenesis showed that 40 proteins were down-regulated and 90 proteins were up-regulated. Proteins were then classified and counted on the basis of their function.

Fig.4

The secretome analysis of insulin resistant skeletal muscle cells showed that 150 proteins were down-regulated and 26 proteins were up-regulated. Proteins were then classified and counted on the basis of their function.

Fig.5

Schematic representation of the secretome of skeletal muscle cells. The stimulation is represented by green arrows and the inhibition is represented by red crossed arrows. Collagens are represented in blue; proteoglycans and glycosaminoglycans are represented in pink; glycoproteins are represented in orange; growth factors and cytokines are represented in purple; enzymes are represented in dark green; enzymatic inhibitors are represented in light green and other proteins are represented in dark gray. MMP: Matrix Metalloproteinase; TIMP: Metalloproteinase inhibitor; IL: Interleukin; IGF: Insulin-like growth factor; FGF: Fibroblast Growth Factor; GDF: Growth/Differentiation factor; GH: Growth hormone; BMP: Bone morphogenetic protein; ENO: Enolase; IGFBP: Insulin-like growth factor binding protein; LTBP: Latent-transforming growth factor beta-binding protein; MCK: Muscle creatine kinase; TGF: Transforming growth factor.

Fig.6

Venn diagrams showing the number of differentially regulated proteins between different conditions/pathologies. A. Proteins differentially regulated between the conditions dystrophin deficiency, atrophy and exercise. B. Proteins differentially regulated between the conditions insulin resistance, myogenesis and insulin stimulation. C. Proteins differentially regulated between the conditions dystrophin deficiency, atrophy and insulin resistance.