The ERK signaling pathway is involved in cardiotrophin-1-induced neural differentiation of human umbilical cord blood mesenchymal stem cells in vitro
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Central nervous system diseases remain the most challenging pathologies, with limited or even no therapeutic possibilities and a poor prognosis. This study aimed to investigate the differentiation properties of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) transfected with recombinant adenovirus expressing enhanced green fluorescence protein cardiotrophin-1 (Adv-EGFP-CT-1) and the possible mechanisms involved. Cells were isolated, and MSC immunophenotypes were confirmed. The resulting differentiated cells treated with Adv-EGFP-CT-1 and cultured in neural induction medium (NIM) expressed higher levels of Nestin, neuronal nuclei (NeuN) and glial fibrillary acidic protein (GFAP) markers than cells in other treatments. Expression of glycoprotein 130/leukemia inhibitory factor receptor β (gp130/LiFRβ), Raf-1, phosphorylated Raf-1 (p-Raf-1), extracellular signal-regulated kinase 1/2 (ERK1/2) and phospho-ERK1/2 (p-ERK1/2) increased gradually within 72 h after transfection with Adv-EGFP-CT-1 and NIM culture. Additionally, inhibition of extracellular signal-regulated kinase kinase (MEK) abrogated expression of p-ERK1/2, Nestin, GFAP and NeuN. Thus, the ERK1/2 pathway may contribute to CT1-stimulated neural differentiation of hUCB-MSCs.
KeywordsCardiotrophin-1 Umbilical cord blood mesenchymal stem cells Neuron-like cells ERK/MAPK signaling pathway
This study was funded by a grant from the National Natural Science Foundation of China (No. 31260286). We are grateful to the doctors and nurses of the Obstetrical Department of Maternity and child health care hospital in Zunyi for the collection of cord blood.
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