Crosstalk between HIF-1 and ROCK pathways in neuronal differentiation of mesenchymal stem cells, neurospheres and in PC12 neurite outgrowth.

Emilie Pacary, Emmanuelle Tixier, Florence Coulet, Simon Roussel, Edwige Petit, Myriam Bernaudin
Molecular and Cellular Neuroscience. 2007-07-01; 35(3): 409-423
DOI: 10.1016/j.mcn.2007.04.002

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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.

Author information:
(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.

DOI: 10.1016/j.mcn.2007.04.002
PMID: 17493827 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus