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Astrocytes induce proliferation of oligodendrocyte progenitor cells via connexin 47-mediated activation of the ERK/Id4 pathway.

Authors: Liu, Zhaoyu  Xu, Dan  Wang, Shang  Chen, Yi  Li, Zhen  Gao, Xiaoyan  Jiang, Lu  Tang, Yong  Peng, Yan 
Citation: Liu Z, etal., Cell Cycle. 2017 Apr 3;16(7):714-722. doi: 10.1080/15384101.2017.1295183. Epub 2017 Feb 22.
Pubmed: (View Article at PubMed) PMID:28278052
DOI: Full-text: DOI:10.1080/15384101.2017.1295183

The proliferative ability of oligodendrocyte progenitor cells (OPCs) varied markedly under different culture conditions. Astrocytes (ASTs) have been verified to play a major role in regulating the proliferation of OPCs through direct contact. However, the mechanisms have not been fully clarified. To investigate the effect and mechanism under AST and OPC co-culture conditions, we analyzed all connexins comprehensively in OPCs under OPC mono-culture, AST-secreted cell factor co-culture and AST-OPC direct-contact co-culture, and found that significantly differentially expressed Cx47 was the most significant. To assess whether Cx47 plays a role in proliferation, Cx47 siRNA were conducted. The result indicates that the cell cycle of OPCs was changed, and the cell proliferation was markedly inhibited. Kyoto Encyclopedia of Genes and Genomes (KEGG) predictive analysis suggested that Cx47 regulate cell cycle and proliferation by Ca(2+) activation of ERK1/2. To verify the prediction, flow cytometry, confocal microscopy, 5-ethynyl-2'-deoxyuridine (EdU), polymerase chain reaction (RT-PCR) and western blot were used. The results show that interference of Cx47 led to decreased Ca(2+) concentrations, lower p-ERK 1/2 levels, reduced transcription factor inhibitor of DNA binding 4 (Id4) expression, arrested cell cycle and reduced OPCs proliferative ability. Additionally, blocking ERK1/2 signaling caused decreased Id4 expression, arrested cell cycle in G1 phase, and reduced OPCs proliferative ability. In conclusion, ASTs can cause Ca(2+) signaling activation, ERK1/2 phosphorylation, and Id4 expression stimulation in OPCs, inducing proliferation of these cells, mainly through Cx47.

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RGD Object Information
RGD ID: 13208599
Created: 2017-08-14
Species: All species
Last Modified: 2017-08-14
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.