**Acknowledgements**

One has to keep in mind, however, that S1P receptors are differently expressed in satellite cells, myoblasts, and muscle fibers, moreover their expression may vary in response to the action of particular factor. PDGF stimulates myoblasts proliferation and motility, while these effects are blocked by SK1/S1P1 signaling axis [126]. In contrast, TGF-β1 was demonstrated to convey its detrimental profibrotic effect through S1P3 receptors (Figure 13) [127]. These observations complement widely known activities of PDGF and TGF-β1 in wound healing. In the second intention healing as it is observed in the severe skeletal muscle injury or late stages of myo‐ pathy, the major role is played by myofibroblasts which cause fibrosis, a hallmark of in which myofibers are replaced by progressive deposition of extracellular matrix proteins [128]. The main task is therefore to facilitate skeletal muscle regeneration rather than repair, as the first one restores tissue structure and contractile function while the latter is limited to structural return. There are efforts observed to improve muscle healing by regeneration rather than fibrosis [129]. Collectively, taking into account the knowledge on how sphingosine 1-phos‐ phate influences RSC and how it might prevent muscle fibrosis, it will be interesting to further

investigate in this context the crosstalk between IGF-1 and S1P signaling pathway.

Primary stem cells in adult skeletal muscle known as satellite cells drive postnatal muscle growth and regeneration-associated hypertrophy. They reside beneath the basal lamina of the myofibers suggesting close contact between the adjacent cytoskeletons and chemical commu‐ nication between the cells. One of the major unexplored areas of satellite cell biology is the identification of signals that are conferred from adjacent myofibers and the surrounding extracellular matrix. Equally important are soluble endocrine, paracrine, and autocrine factors that maintain satellite cells quiescent and control their preference to activate. For example, the maintenance of skeletal muscle requires notch signaling and greatly depends on delta upregulation for RSC activation [130]. In addition to the loss of notch activation, nonregener‐ ating skeletal muscle produces excessive transforming growth factor (TGF)-β (but not myostatin), which induces unusually high levels of TGF-β pSmad3 and interferes with their regenerative capacity [131]. Thus a balance between endogenous pSmad3 and active notch controls the regenerative competence of muscle stem cells, and the deregulation of this balance in the old muscle microniche interferes with regeneration. The molecular mechanisms that regulate satellite cell quiescence, activation, and self renewal (asymmetric divisions) are not well understood, even though a possible clue for the ambiguous behavior of satellite cells could be associated with the membrane segregation of rafts and bioactive lipids such as PS that seems to accelerate myoblasts fusion into myotubes [132]. It seems plausible to affirm sarcolemmal differentiation as the leader constituent of stimulated skeletal muscle progenitors and subse‐ quent populations of daughter cells (myoblasts, myotubes, and juvenile myofibers) involved in myogenic program. Lipid moiety of plasma membrane is not merely a boundary or the component in intercellular communication. Nowadays, it is widely accepted that specific lipids associate to form functional units (LR/C), creating substructures that actively modify its own composition including proteins and triggering a myriad of different signaling pathways. Lipid

**12. Concluding remarks**

130 Muscle Cell and Tissue

Support for this work was provided by grant No UMO-2013/11/B/NZ5/03106 from the National Science Centre in Poland.
