Crosstalk between HIF-1 and ROCK pathways in neuronal differentiation of mesenchymal stem cells, neurospheres and in PC12 neurite outgrowth.
Molecular and Cellular Neuroscience. 2007-07-01; 35(3): 409-423
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1. Mol Cell Neurosci. 2007 Jul;35(3):409-23. Epub 2007 Apr 10.
Crosstalk between HIF-1 and ROCK pathways in neuronal differentiation of
mesenchymal stem cells, neurospheres and in PC12 neurite outgrowth.
Pacary E(1), Tixier E, Coulet F, Roussel S, Petit E, Bernaudin M.
(1)UMR-CNRS 6185, Hypoxia and Cerebrovascular Physiopathology Group, University
of Caen, CYCERON, Bd Henri Becquerel, BP 5229, F-14074 Caen cedex, France.
This study demonstrates that the Rho-kinase (ROCK) inhibitor, Y-27632,
potentiates not only the effect of cobalt chloride (CoCl(2)) but also that of
deferoxamine, another HIF-1 inducer, on mesenchymal stem cell (MSC) neuronal
differentiation. HIF-1 is essential for CoCl(2)+/-Y-27632-induced MSC neuronal
differentiation, since agents inhibiting HIF-1 abolish the changes of morphology
and cell cycle arrest-related gene or protein expressions (p21, cyclin D1) and
the increase of neuronal marker expressions (Tuj1, NSE). Y-27632 potentiates the
CoCl(2)-induced decrease of cyclin D1 and nestin expressions, the increase of
HIF-1 activation and EPO expression, and decreases pVHL expression.
Interestingly, CoCl(2) decreases RhoA expression, an effect potentiated by
Y-27632, revealing crosstalk between HIF-1 and RhoA/ROCK pathways. Moreover, we
demonstrate a synergistic effect of CoCl(2) and Y-27632 on neurosphere
differentiation into neurons and PC12 neurite outgrowth underlining that a
co-treatment targeting both HIF-1 and ROCK pathways might be relevant to
differentiate stem cells into neurons.
PMID: 17493827 [Indexed for MEDLINE]