The sonic hedgehog pathway mediates carbamylated erythropoietin-enhanced proliferation and differentiation of adult neural progenitor cells
| Autor: | Rui Lan Zhang, Marcel Leist, Constance Tom Noguchi, Lars Torup, Sara R Gregg, Xianshuang Liu, Zhongxian Jiao, Yifan Feng, Zheng Gang Zhang, Zhi-Yong Chen, Michael Chopp, Jens Gerwien, Lei Wang, Yvonne LeTourneau |
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| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Male
medicine.medical_specialty animal structures Cyclopamine Cellular differentiation Subventricular zone Biochemistry Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine ddc:570 Basic Helix-Loop-Helix Transcription Factors Receptors Erythropoietin medicine Animals Hedgehog Proteins Sonic hedgehog Progenitor cell Erythropoietin Molecular Biology Cell Proliferation 030304 developmental biology 0303 health sciences Base Sequence biology Neurogenesis Cell Differentiation Cell Biology Neural stem cell Hedgehog signaling pathway Up-Regulation Cell biology Adult Stem Cells medicine.anatomical_structure Endocrinology chemistry biology.protein 030217 neurology & neurosurgery Signal Transduction |
| Popis: | Carbamylated erythropoietin (CEPO), a well characterized erythropoietin (EPO) derivative, does not bind to the classical EPO receptor and does not stimulate erythropoiesis. Using neural progenitor cells derived from the subventricular zone of the adult mouse, we investigated the effect of CEPO on neurogenesis and the associated signaling pathways in vitro. We found that CEPO significantly increased neural progenitor cell proliferation and promoted neural progenitor cell differentiation into neurons, which was associated with up-regulation of Sonic hedgehog (Shh), its receptor ptc, and mammalian achaete-scute homolog 1 (Mash1), a pro-neuron basic helix-loop-helix protein transcription factor. Blockage of the Shh signaling pathway with a pharmacological inhibitor, cyclopamine, abolished the CEPO-induced neurogenesis. Attenuation of endogenous Mash1 expression by short-interfering RNA blocked CEPO-promoted neuronal differentiation. In addition, recombinant mouse Shh up-regulated Mash1 expression in neural progenitor cells. These results demonstrate that the Shh signaling pathway mediates CEPO-enhanced neurogenesis and Mash1 is a downstream target of the Shh signaling pathway that regulates CEPO-enhanced neuronal differentiation. |
| Databáze: | OpenAIRE |
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