Abstract
Tissue damage, irrespective from the underlying etiology, destroys tissue structure and, eventually, function. In attempt to achieve a morpho-functional recover of the damaged tissue, reparative/regenerative processes start in those tissues endowed with regenerative potential, mainly mediated by activated resident stem cells. These cells reside in a specialized niche that includes different components, cells and surrounding extracellular matrix (ECM), which, reciprocally interacting with stem cells, direct their cell behavior. Evidence suggests that ECM stiffness represents an instructive signal for the activation of stem cells sensing it by various mechanosensors, able to transduce mechanical cues into gene/protein expression responses. The actin cytoskeleton network dynamic acts as key mechanotransducer of ECM signal. The identification of signaling pathways influencing stem cell mechanobiology may offer therapeutic perspectives in the regenerative medicine field. Sphingosine 1-phosphate (S1P)/S1P receptor (S1PR) signaling, acting as modulator of ECM, ECM-cytoskeleton linking proteins and cytoskeleton dynamics appears a promising candidate. This review focuses on the current knowledge on the contribution of S1P/S1PR signaling in the control of mechanotransduction in stem/progenitor cells. The potential contribution of S1P/S1PR signaling in the mechanobiology of skeletal muscle stem cells will be argued based on the intriguing findings on S1P/S1PR action in this mechanically dynamic tissue.
Highlights
The capability of adult tissues to repair and regenerate after damage strictly depends on the functionality of resident stem cells
Evidence suggests that extracellular matrix (ECM) stiffness represents an instructive signal for the activation of stem cells sensing it by various mechanosensors, able to transduce mechanical cues into gene/protein expression responses
This review focuses on the current knowledge on the contribution of Sphingosine 1-phosphate (S1P)/S1P receptor (S1PR) signaling in the control of mechanotransduction in stem/progenitor cells
Summary
The capability of adult tissues to repair and regenerate after damage strictly depends on the functionality of resident stem cells. The cells are capable of sensing mechanical stimuli from the surrounding microenvironment mainly thanks to the dynamics of several surface components, defined mechanosensors, including, among others, transmembrane receptor, focal adhesion (FA) proteins, transmembrane mechanosensitive channels and mechanosensitive transcriptional factors They can convert those stimuli into biochemical cascades leading to gene/protein expression [9,14,15,16]. It is worth mentioning that mechanical forces of ECM affect the behavior of stem cells in terms of survival, proliferation, migration and differentiation, and in their ability to modulate, in a reciprocal manner, the deposition, composition, rearrangement or removal of ECM and to exert force on it This with the aim of maintaining the desired biomechanical properties of ECM, which enable stem cell proper functionality [3,15,21]. Part of this review will be eventually devoted to the potential contribution of S1P/S1PR signaling in regulating the mechanobiology of satellite cells, the widely regarded resident skeletal muscle stem cells, based on the intriguing findings on S1P action in this mechanically dynamic tissue
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