The Sonic Hedgehog Pathway Mediates Carbamylated Erythropoietin-enhanced Proliferation and Differentiation of Adult Neural Progenitor Cells

• DOI: 10.1074/jbc.m706880200
• Publication Date: 2007-09-06T00:13:46Z
• Authors: Lei Wang; Zheng Gang Zhang; Sara R. Gregg; Rui Lan Zhang; Zhongxian Jiao; Yvonne LeTourneau; Xianshuang Liu; Yifan Feng; Jens Gerwien; Lars Torup; Marcel Leist; Constance Tom Nog...; Zhi-Yong Chen; Michael Chopp
• Keywords: Progenitor; Neural Development

Carbamylated erythropoietin (CEPO), a well characterized (EPO) derivative, does not bind to the classical EPO receptor and stimulate erythropoiesis. Using neural progenitor cells derived from subventricular zone of adult mouse, we investigated effect CEPO on neurogenesis associated signaling pathways in vitro. We found that significantly increased cell proliferation promoted differentiation into neurons, which was with up-regulation Sonic hedgehog (Shh), its ptc, mammalian achaete-scute homolog 1 (Mash1), pro-neuron basic helix-loop-helix protein transcription factor. Blockage Shh pathway pharmacological inhibitor, cyclopamine, abolished CEPO-induced neurogenesis. Attenuation endogenous Mash1 expression by short-interfering RNA blocked CEPO-promoted neuronal differentiation. In addition, recombinant mouse up-regulated cells. These results demonstrate mediates CEPO-enhanced is downstream target regulates