Extracellular Hsp70 Enhances Mesoangioblast Migration via an Autocrine Signaling Pathway

Fabiana Geraci, Rosaria Tinnirello, Gabriella Sconzo, Walter Spinello, Maria Magdalena Barreca, Vincenzo Cavalieri, Giuseppina Turturici, Rosaria Tinnirello, Punit Kaur, Fabiana Geraci, Alexzander A. A. Asea

Risultato della ricerca: Articlepeer review

11 Citazioni (Scopus)

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).
Lingua originaleEnglish
pagine (da-a)1845-1861
Numero di pagine17
RivistaJournal of Cellular Physiology
Volume232
Stato di pubblicazionePublished - 2017

All Science Journal Classification (ASJC) codes

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  • ???subjectarea.asjc.1300.1308???
  • ???subjectarea.asjc.1300.1307???

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