Stimulation of α1-adrenoceptor or angiotensin type 1 receptor enhances DNA synthesis in human-induced pluripotent stem cells via Gq-coupled receptor-dependent signaling pathways

Abstract

Stimulation of either α1-adrenoceptor or angiotensin type 1 receptor (AT1 receptor) induces proliferation of mouse induced pluripotent stem (iPS) cells. Both α1-adrenoceptor and AT1 receptor are guanine nucleotide-binding protein q polypeptide (Gq)-coupled receptors. However, it is not fully understood whether stimulation of these Gq-coupled receptors exert a similar effect in human iPS cells, i.e. proliferation of human iPS cells. In this study, we evaluated the involvement of α1-adrenoceptor and AT1 receptor in the DNA synthesis of human iPS cells. Treatment with either l-phenylephrine (a selective α1-adrenoceptor agonist) or angiotensin II (Ang II) significantly increased DNA synthesis in human iPS cells. Enhanced DNA synthesis was significantly inhibited by pretreatment with protein kinase C (PKC) inhibitors, mitogen-activated protein kinase kinase (MEK) inhibitor, or phosphatidylinositol-3 phosphate kinase (PI3K) inhibitor. Treatment with either l-phenylephrine or Ang II significantly increased Akt and p44/42 MAPK phosphorylation. Short interfering RNA (siRNA) directed against Gq significantly inhibited DNA synthesis and phosphorylation of Akt and p44/42 MAPK enhanced by l-phenylephrine or Ang II. These results suggest that stimulation of α1-adrenoceptor or AT1 receptor may enhance DNA synthesis in human iPS cells via Gq-coupled receptor-dependent signaling pathways.