Another function of Hsp70 in mesoangioblast stem cells

In recent years, it has been demonstrated that Hsp70 is released in the extracellular space under normal cell culture conditions, and this release is mediated through exosomes. We have demonstrated that A6 cells, a clone of mouse mesoangioblasts, produce and release in the extracellular space membrane vesicles, independently of culture growth conditions. These vesicles contains both structural proteins and biological active molecules, such as FGF-2 and the metalloproteinases MMP 2 and 9. We have also demonstrated that A6 vesicles contain HspP70 and its release is highly regulated. Some of the intracellular Hsp70 is localized on lipid rafts and its concentration in insoluble fraction increases after heat shock. Vesicle shedding is influenced by lipid raft integrity, but not so Hsp70 release. Recent experiments have demonstrated that A6 vesicles also contain urokinase and tissue-type plasminogen activators (uPA and tPA), both responsible of plasmin activation. These two proteins could be responsible for MMP activation, as reported in other cell lines. Recently it has been demonstrated that MMP9 expression depends on Hsp70, through NF-kB and AP1 activation. Our preliminary data demonstrated that NM3 cells, a clone with a 55% Hsp70 knockdown, release an increased level of MMP 2/9 in the milieu. Therefore, it is possible to hypothesize a negative role of Hsp70 in MMP expression, in addition with its previously demonstrated role in cell proliferation. The data we have obtained on A6 vesicles also demonstrated that they contain RNA, both mRNA and miRNA, and they are able to be phagocytated by target cells