Cell-free DNA fragments increase transcription in human mesenchymal stem cells, activate tlr-dependent signal pathway and supress apoptosis

Kostyuk S.V.1 , Malinovskaya E.M.1, Ermakov A.V.1, Smirnova T.D.1, Kameneva L.V.1, Chvartatskaya O.V.1, Loseva P.A.1, Ershova E.S.1, Lyubchenko L.N.2, Veiko N.N.1

1. Research Centre for Medical Genetics, Russian Academy of Medical Sciences
2. Blokhin Cancer Research Center, Russian Academy of Medical Sciences
Section: Experimental/Clinical Study
DOI: 10.18097/pbmc20125806673      UDK: 577.218      PubMed Id: 23350199
Year: 2012  Volume: 58  Issue: 6  Pages: 673-683
Human mesenchymal stem cells (MSCs) are now widely adopted in regenerative medicine. However, many questions on the role of different signaling pathways in the regulation of stem cell (SC) functional activity within the organism remain unaswered. In damaged regions the level of cell death increases and DNA fragments from dead cells (cell-free DNA, cfDNA) are accumulated in blood. We showed that in adipose-derived MSCs exposed in vitro to cfDNA fragments the transcription level increased (the total amount of cellular RNA and the rRNA amount rose). GC-rich CfDNA fragments (GC-DNA) activated the TLR9-dependent signal pathway: the expression of TLR9 and of TLR9-signaling pathway adapter - MyD88 - was up-regulated. AT-rich DNA fragments did not increase the TLR9 expression, though, the MyD88 expression level rose. So we suggest that AT-DNA acts via some other receptors that nevertheless activate MyD88-dependent signalling in MSCs. We also showed that cfDNA fragments decreased the activity of caspase, an apoptotic enzyme. So, cfDNA can significantly influence the functional activity of MSC by activating TLR9- and MyD88-dependent signal pathways and lowering the apoptosis level.
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Kostyuk S.V., Malinovskaya E.M., Ermakov A.V., Smirnova T.D., Kameneva L.V., Chvartatskaya O.V., Loseva P.A., Ershova E.S., Lyubchenko L.N., Veiko N.N. (2012) Biomeditsinskaya khimiya, 58(6), 673-683.
This paper is also available as the English translation:10.1134/S1990750812010052
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