title: Extracellular Hsp70 Enhances Mesoangioblast Migration via an Autocrine Signaling Pathway.
abstract: Mouse mesoangioblasts are vessel-associated progenitor stem cells endowed with the ability of multipotent mesoderm differentiation. Therefore, they represent a promising tool in the regeneration of injured tissues. Several studies have demonstrated that homing of mesoangioblasts into blood and injured tissues are mainly controlled by cytokines/chemokines and other inflammatory factors. However, little is known about the molecular mechanisms regulating their ability to traverse the extracellular matrix (ECM). Here, we demonstrate that membrane vesicles released by mesoangioblasts contain Hsp70, and that the released Hsp70 is able to interact by an autocrine mechanism with Toll-like receptor 4 (TLR4) and CD91 to stimulate migration. We further demonstrate that Hsp70 has a positive role in regulating matrix metalloproteinase 2 (MMP2) and MMP9 expression and that MMP2 has a more pronounced effect on cell migration, as compared to MMP9. In addition, the analysis of the intracellular pathways implicated in Hsp70 regulated signal transduction showed the involvement of both PI3K/AKT and NF-κB. Taken together, our findings present a paradigm shift in our understanding of the molecular mechanisms that regulate mesoangioblast stem cells ability to traverse the extracellular matrix (ECM). J. Cell. Physiol. 232: 1845-1861, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, Palermo, Italy.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Barreca
authors.affiliation: Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, Palermo, Italy.
authors.forename: Walter
authors.initials: W
authors.lastname: Spinello
authors.affiliation: Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, Palermo, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cavalieri
authors.affiliation: Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, Palermo, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Turturici
authors.affiliation: Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, Palermo, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Sconzo
authors.affiliation: Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, Georgia.
authors.forename: Punit
authors.initials: P
authors.lastname: Kaur
authors.affiliation: Biomedicine and Molecular Immunology Institute, National Center of Research, Palermo, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Tinnirello
authors.affiliation: Department of Neurology and the Deanship for Scientific Research, University of Dammam, Dammam, Saudi Arabia.
authors.forename: Alexzander A A
authors.initials: AA
authors.lastname: Asea
authors.affiliation: Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, Palermo, Italy.|Euro-Mediterranean Institute of Science and Technology, Palermo, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Geraci
mesh_terms: D000818:Animals; D019898:Autocrine Communication; D002465:Cell Movement; D042783:Endothelial Cells; D005110:Extracellular Space / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D021962:Membrane Microdomains / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D018840:HSP70 Heat-Shock Proteins; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D016328:NF-kappa B; D051197:Toll-Like Receptor 4; D000072000:NF-KappaB Inhibitor alpha; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9