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Sphingosylphosphorylcholine induces differentiation of human mesenchymal stem cells into smooth-muscle-like cells through a TGF-beta-dependent mechanism.
J Cell Sci. 2006 Dec 01; 119(Pt 23):4994-5005.JC

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 alpha-smooth-muscle actin (alpha-SMA), h1-calponin and SM22alpha, as effectively as transforming growth factor beta (TGF-beta1) and TGF-beta3. SPC elicited delayed phosphorylation of Smad2 after 24 hours exposure, in contrast to rapid phosphorylation of Smad2 induced by TGF-beta treatment for 10 minutes. Pretreatment of the cells with pertussis toxin or U0126, an MEK inhibitor, markedly attenuated the SPC-induced expression of beta-SMA and delayed phosphorylation of Smad2, suggesting that the Gi/o-ERK pathway is involved in the increased expression of alpha-SMA through induction of delayed Smad2 activation. In addition, SPC increased secretion of TGF-beta1 through an ERK-dependent pathway, and the SPC-induced expression of alpha-SMA and delayed phosphorylation of Smad2 were blocked by SB-431542, a TGF-beta type I receptor kinase inhibitor, or anti-TGF-beta1 neutralizing antibody. Silencing of Smad2 expression with small interfering RNA (siRNA) abrogated the SPC-induced expression of alpha-SMA. These results suggest that SPC-stimulated secretion of TGF-beta1 plays a crucial role in SPC-induced smooth muscle cell (SMC) differentiation through a Smad2-dependent pathway. Both SPC and TGF-beta 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 alpha-SMA expression induced by SPC or TGF-beta. These results suggest that SPC induces differentiation of hATSCs to smooth-muscle-like cell types through G(i/o)-ERK-dependent autocrine secretion of TGF-beta, which activates a Smad2-SRF/myocardin-dependent pathway.

Authors+Show Affiliations

Medical Research Center for Ischemic Tissue Regeneration of Pusan National University and the Medical Research Institute, College of Medicine, Pusan National University, Busan 602-739, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17105765

Citation

Jeon, Eun Su, et al. "Sphingosylphosphorylcholine Induces Differentiation of Human Mesenchymal Stem Cells Into Smooth-muscle-like Cells Through a TGF-beta-dependent Mechanism." Journal of Cell Science, vol. 119, no. Pt 23, 2006, pp. 4994-5005.
Jeon ES, Moon HJ, Lee MJ, et al. Sphingosylphosphorylcholine induces differentiation of human mesenchymal stem cells into smooth-muscle-like cells through a TGF-beta-dependent mechanism. J Cell Sci. 2006;119(Pt 23):4994-5005.
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-beta-dependent mechanism. Journal of Cell Science, 119(Pt 23), 4994-5005.
Jeon ES, et al. Sphingosylphosphorylcholine Induces Differentiation of Human Mesenchymal Stem Cells Into Smooth-muscle-like Cells Through a TGF-beta-dependent Mechanism. J Cell Sci. 2006 Dec 1;119(Pt 23):4994-5005. PubMed PMID: 17105765.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sphingosylphosphorylcholine induces differentiation of human mesenchymal stem cells into smooth-muscle-like cells through a TGF-beta-dependent mechanism. AU - Jeon,Eun Su, AU - Moon,Hyun Jung, AU - Lee,Mi Jeong, AU - Song,Hae Young, AU - Kim,Young Mi, AU - Bae,Yong Chan, AU - Jung,Jin Sup, AU - Kim,Jae Ho, Y1 - 2006/11/14/ PY - 2006/11/16/pubmed PY - 2007/4/7/medline PY - 2006/11/16/entrez SP - 4994 EP - 5005 JF - Journal of cell science JO - J Cell Sci VL - 119 IS - Pt 23 N2 - 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 alpha-smooth-muscle actin (alpha-SMA), h1-calponin and SM22alpha, as effectively as transforming growth factor beta (TGF-beta1) and TGF-beta3. SPC elicited delayed phosphorylation of Smad2 after 24 hours exposure, in contrast to rapid phosphorylation of Smad2 induced by TGF-beta treatment for 10 minutes. Pretreatment of the cells with pertussis toxin or U0126, an MEK inhibitor, markedly attenuated the SPC-induced expression of beta-SMA and delayed phosphorylation of Smad2, suggesting that the Gi/o-ERK pathway is involved in the increased expression of alpha-SMA through induction of delayed Smad2 activation. In addition, SPC increased secretion of TGF-beta1 through an ERK-dependent pathway, and the SPC-induced expression of alpha-SMA and delayed phosphorylation of Smad2 were blocked by SB-431542, a TGF-beta type I receptor kinase inhibitor, or anti-TGF-beta1 neutralizing antibody. Silencing of Smad2 expression with small interfering RNA (siRNA) abrogated the SPC-induced expression of alpha-SMA. These results suggest that SPC-stimulated secretion of TGF-beta1 plays a crucial role in SPC-induced smooth muscle cell (SMC) differentiation through a Smad2-dependent pathway. Both SPC and TGF-beta 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 alpha-SMA expression induced by SPC or TGF-beta. These results suggest that SPC induces differentiation of hATSCs to smooth-muscle-like cell types through G(i/o)-ERK-dependent autocrine secretion of TGF-beta, which activates a Smad2-SRF/myocardin-dependent pathway. SN - 0021-9533 UR - https://www.unboundmedicine.com/medline/citation/17105765/Sphingosylphosphorylcholine_induces_differentiation_of_human_mesenchymal_stem_cells_into_smooth_muscle_like_cells_through_a_TGF_beta_dependent_mechanism_ DB - PRIME DP - Unbound Medicine ER -