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Sphingosylphosphorylcholine induces differentiation of human mesenchymal stem cells into smooth-muscle-like cells through a TGF-β-dependent mechanism
Abstract
Mesenchymal stem cells (MSCs) can differentiate into diverse cell types including adipogenic, osteogenic, chondrogenic and myogenic lineages. In the present study, we demonstrated for the first time that sphingosylphosphorylcholine (SPC) induces differentiation of human adipose-tissue-derived mesenchymal stem cells (hATSCs) to smooth-muscle-like cell types. SPC increased the expression levels of several smooth-muscle-specific genes, such as those for α-smooth-muscle actin (α-SMA), h1-calponin and SM22α, as effectively as transforming growth factor β (TGF-β1) and TGF-β3. SPC elicited delayed phosphorylation of Smad2 after 24 hours exposure, in contrast to rapid phosphorylation of Smad2 induced by TGF-β treatment for 10 minutes. Pretreatment of the cells with pertussis toxin or U0126, an MEK inhibitor, markedly attenuated the SPC-induced expression of β-SMA and delayed phosphorylation of Smad2, suggesting that the Gi/o-ERK pathway is involved in the increased expression of α-SMA through induction of delayed Smad2 activation. In addition, SPC increased secretion of TGF-β1 through an ERK-dependent pathway, and the SPC-induced expression of α-SMA and delayed phosphorylation of Smad2 were blocked by SB-431542, a TGF-β type I receptor kinase inhibitor, or anti-TGF-β1 neutralizing antibody. Silencing of Smad2 expression with small interfering RNA (siRNA) abrogated the SPC-induced expression of α-SMA. These results suggest that SPC-stimulated secretion of TGF-β1 plays a crucial role in SPC-induced smooth muscle cell (SMC) differentiation through a Smad2-dependent pathway. Both SPC and TGF-β increased the expression levels of serum-response factor (SRF) and myocardin, transcription factors involved in smooth muscle differentiation. siRNA-mediated depletion of SRF or myocardin abolished the α-SMA expression induced by SPC or TGF-β. These results suggest that SPC induces differentiation of hATSCs to smooth-muscle-like cell types through Gi/o-ERK-dependent autocrine secretion of TGF-β, which activates a Smad2-SRF/myocardin-dependent pathway.
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Cites
Smad3 Mediates Transforming Growth Factor-β–Induced α-Smooth Muscle Actin Expression
Hu, B., Wu, Z., & Phan, S. H. (2003) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2003-0063oc · Cited by 325
Cited by
Adipose-derived stem cells for regenerative medicine
Gimble, J. M., Katz, A. J., & Bunnell, B. A. (2007) · Circulation Research · doi:10.1161/01.res.0000265074.83288.09 · Cited by 2,332
Bone Marrow Mesenchymal Stem Cells: Historical Overview and Concepts
Charbord, P. (2010) · Human Gene Therapy · doi:10.1089/hum.2010.115 · Cited by 441
Kramann, R., Goettsch, C., Wongboonsin, J., Iwata, H., Schneider, R. K., Kuppe, C., Kaesler, N., Chang-Panesso, M., Machado, F. G., Gratwohl, S., et al. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.08.001 · Cited by 308
Kim, Y. J., Kim, H. K., Cho, H. H., Bae, Y. C., Suh, K. T., & Jung, J. S. (2007) · Cellular Physiology and Biochemistry · doi:10.1159/000110447 · Cited by 298
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Visconti, R. P., Kasyanov, V., Gentile, C., Zhang, J., Markwald, R. R., & Mironov, V. (2010) · Expert Opinion on Biological Therapy · doi:10.1517/14712590903563352 · Cited by 224
Metadata
- Authors
- Jeon, E. S., Moon, H. J., Lee, M. J., Song, H. Y., Kim, Y. M., Bae, Y. C., Jung, J. S., & Kim, J. H.
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2006-12-01
- Volume
- 119
- Issue
- 23
- Pages
- 4994-5005
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W2052426301
- Cited by
- 162
- References
- 1
- FWCI
- 4.52
- Type
- journal article
- Language
- en
- Open access
- closed
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- CoChat. (2026). Citation check: Sphingosylphosphorylcholine induces differentiation of human mesenchymal stem cells into smooth-muscle-like cells through a TGF-β-dependent mechanism. https://app.cochat.ai/papers/10.1242/jcs.03281
- The paper
- Jeon, E. S., Moon, H. J., Lee, M. J., Song, H. Y., Kim, Y. M., Bae, Y. C., Jung, J. S., & Kim, J. H. (2006). Sphingosylphosphorylcholine induces differentiation of human mesenchymal stem cells into smooth-muscle-like cells through a TGF-β-dependent mechanism. Journal of Cell Science. https://doi.org/10.1242/jcs.03281
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