Hypoxia-induced proliferation in mesenchymal stem cells and angiotensin II-mediated PI3K/AKT pathway

Hypoxia could stimulate proliferation of mesenchymal stem cells (MSCs) under certain conditions. This study determined angiotensin II mechanisms and PI3K/AKT pathway in hypoxia-induced proliferation of MSCs. Hypoxia (3% oxygen) induced cellular proliferation in mouse MSCs and upregulated endogenous angiotensin II and angiotensin-converting enzyme in the cell culture and expression of AT1 receptors. The expressions of Sox2, not Oct4 and Rex1, were significantly increased by the hypoxia. The blockade of AT1 receptors, not AT2 receptors, depressed hypoxia induced the proliferative effects. Both hypoxia and exogenous angiotensin II activated p-AKT. Moreover, AT1 receptor inhibitor blocked the effects of hypoxia-mediated p-AKT upregulation. The data demonstrated that the hypoxia at 3% oxygen level could induce mouse MSC proliferation, probably as a result of the activation of PI3K signalling pathways via AT1 receptors. Copyright (c) 2015 John Wiley & Sons, Ltd.