Sphingosine 1-Phosphate Receptor 1 Is Required for MMP-2 Function in Bone Marrow Mesenchymal Stromal Cells: Implications for Cytoskeleton Assembly and Proliferation. (11th March 2018)

• Record Type: Journal Article
• Authors: Sassoli, Chiara; Pierucci, Federica; Tani, Alessia; Frati, Alessia; Chellini, Flaminia; Matteini, Francesca; Vestri, Ambra; Anderloni, Giulia; Nosi, Daniele; Zecchi-Orlandini, Sandra; Meacci, Elisabetta
• Other Names: Brunelli Silvia Academic Editor.
• Is Part Of: Stem cells international. Volume 2018(2018)
• Publication Date: 2018-03-11
• Subjects: Stem Cells -- Periodicals; Stem Cells -- Therapeutic use -- Periodicals; Stem Cells -- Transplantation -- Periodicals; 616.0277405
• DOI: 10.1155/2018/5034679
• Languages: English
• ISSNs: 1687-966X

Abstract

Abstract : Bone marrow-derived mesenchymal stromal cell- (BM-MSC-) based therapy is a promising option for regenerative medicine. An important role in the control of the processes influencing the BM-MSC therapeutic efficacy, namely, extracellular matrix remodelling and proliferation and secretion ability, is played by matrix metalloproteinase- (MMP-) 2. Therefore, the identification of paracrine/autocrine regulators of MMP-2 function may be of great relevance for improving BM-MSC therapeutic potential. We recently reported that BM-MSCs release the bioactive lipid sphingosine 1-phosphate (S1P) and, here, we demonstrated an impairment of MMP-2 expression/release when the S1P receptor subtype S1PR1 is blocked. Notably, active S1PR1/MMP-2 signalling is required for F-actin structure assembly (lamellipodia, microspikes, and stress fibers) and, in turn, cell proliferation. Moreover, in experimental conditions resembling the damaged/regenerating tissue microenvironment (hypoxia), S1P/S1PR1 system is also required for HIF-1 α expression and vinculin reduction. Our findings demonstrate for the first time the trophic role of S1P/S1PR1 signalling in maintaining BM-MSCs' ability to modulate MMP-2 function, necessary for cytoskeleton reorganization and cell proliferation in both normoxia and hypoxia. Altogether, these data provide new perspectives for considering S1P/S1PR1 signalling a pharmacological target to preserve BM-MSC properties and to potentiate their beneficial potential in tissue repair.