GDF11 induces differentiation and apoptosis and inhibits migration of C17.2 neural stem cells via modulating MAPK signaling pathway
- Published
- Accepted
- Subject Areas
- Biochemistry, Bioinformatics, Cell Biology, Neuroscience, Evidence Based Medicine
- Keywords
- Growth differentiation factor 11, C17.2 neural stem cells, differentiation, apoptosis, MAPK signaling pathway, migration
- Copyright
- © 2018 Wang et al.
- Licence
- This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ Preprints) and either DOI or URL of the article must be cited.
- Cite this article
- 2018. GDF11 induces differentiation and apoptosis and inhibits migration of C17.2 neural stem cells via modulating MAPK signaling pathway. PeerJ Preprints 6:e27003v1 https://doi.org/10.7287/peerj.preprints.27003v1
Abstract
GDF11, a member of TGF-β superfamily, has recently received widespread attention as a novel anti-ageing/rejuvenation factor to reverse age-related dysfunctions in heart and skeletal muscle, and to induce angiogenesis and neurogenesis. However, these positive effects of GDF11 were challenged by several other studies. Furthermore, the mechanism is still not well understood. In the present study, we evaluated the effects and underlying mechanisms of GDF11 on C17.2 neural stem cells. GDF11 induced differentiation and apoptosis, and suppressed migration of C17.2 neural stem cells. Besides, GDF11 slightly increased cell viability after 24h treatment, showed no effects on proliferation for about 10 days of cultivation, and slightly decreased cumulative population doubling for long-term treatment (p<0.05). Phospho-proteome profiling array displayed that GDF11 significantly increased the phosphorylation level of 13 serine/threonine kinases (p<0.01), including p-p38, p-ERK and p-Akt, in C17.2 cells, which implied the activation of MAPK pathway. Western blot validated that the results of phospho-proteome profiling array were reliable. Based on functional analysis, we demonstrated that the differentially expressed proteins were mainly involved in signal transduction which was implicated in cellular behavior. Collectively, our findings suggest that, for neurogenesis, GDF11 might not be the desired rejuvenation factor, but a potential target for pharmacologic blockade.
Author Comment
This is a submission to PeerJ for review.
Supplemental Information
The details of the Human Phospho-MAPK Array coordinates
KEGG pathway enrichment of differentially expressed proteins
The morphology of C17.2 cells treated with indicated concentrations of GDF11
Images were obtainedat 50Xmagnification by inverted fluorescence microscope. The live cells were stained with calcein AM in green, and the dead cells were stained with EthD-1 in red.