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Migration of human umbilical cord blood mesenchymal stem cells mediated by stromal cell-derived factor-1/CXCR4 axis via Akt, ERK, and p38 signal transduction pathways.
Biochem Biophys Res Commun 2010; 398(1):105-10BB

Abstract

Human mesenchymal stem cells (hMSCs) have been used for cell-based therapies in degenerative disease and as vehicles for delivering therapeutic genes to sites of injury and tumors. Recently, umbilical cord blood (UCB) was identified as a source for MSCs, and human UCB-derived MSCs (hUCB-MSCs) can serve as an alternative source of bone marrow-derived mesenchymal stem cells (BM-MSCs). However, migration signaling pathways required for homing and recruitment of hUCB-MSCs are not fully understood. Stromal cell-derived factor-1 (SDF-1), a ligand for the CXCR4 chemokine receptor, plays a pivotal role in mobilization and homing of stem cells and modulates different biological responses in various stem cells. In this study, expression of CXCR4 in hUCB-MSCs was studied by western blot analysis and the functional role of SDF-1 was assessed. SDF-1 induced the migration of hUCB-MSCs in a dose-dependent manner. The induced migration was inhibited by the CXCR4-specific peptide antagonist (AMD3100) and by inhibitors of phosphoinositide 3-kinase (LY294002), mitogen-activated protein kinase/extracellular signal related kinase (PD98059) and p38MAPK inhibitor (SB203580). hUCB-MSCs treated with SDF-1 displayed increased phosphorylation of Akt, ERK and p38, which were inhibited by AMD3100. Small-interfering RNA-mediated knock-down of Akt, ERK and p38 blocked SDF-1 induced hUCB-MSC migration. In addition, SDF-1-induced actin polymerization was also blocked by these inhibitors. Taken together, these results demonstrate that Akt, ERK and p38 signal transduction pathways may be involved in SDF-1-mediated migration of hUCB-MSCs.

Authors+Show Affiliations

Department of Biomedical Science, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.No affiliation info availableNo affiliation info availableNo 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

20558135

Citation

Ryu, Chung Heon, et al. "Migration of Human Umbilical Cord Blood Mesenchymal Stem Cells Mediated By Stromal Cell-derived factor-1/CXCR4 Axis Via Akt, ERK, and P38 Signal Transduction Pathways." Biochemical and Biophysical Research Communications, vol. 398, no. 1, 2010, pp. 105-10.
Ryu CH, Park SA, Kim SM, et al. Migration of human umbilical cord blood mesenchymal stem cells mediated by stromal cell-derived factor-1/CXCR4 axis via Akt, ERK, and p38 signal transduction pathways. Biochem Biophys Res Commun. 2010;398(1):105-10.
Ryu, C. H., Park, S. A., Kim, S. M., Lim, J. Y., Jeong, C. H., Jun, J. A., ... Jeun, S. S. (2010). Migration of human umbilical cord blood mesenchymal stem cells mediated by stromal cell-derived factor-1/CXCR4 axis via Akt, ERK, and p38 signal transduction pathways. Biochemical and Biophysical Research Communications, 398(1), pp. 105-10. doi:10.1016/j.bbrc.2010.06.043.
Ryu CH, et al. Migration of Human Umbilical Cord Blood Mesenchymal Stem Cells Mediated By Stromal Cell-derived factor-1/CXCR4 Axis Via Akt, ERK, and P38 Signal Transduction Pathways. Biochem Biophys Res Commun. 2010 Jul 16;398(1):105-10. PubMed PMID: 20558135.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Migration of human umbilical cord blood mesenchymal stem cells mediated by stromal cell-derived factor-1/CXCR4 axis via Akt, ERK, and p38 signal transduction pathways. AU - Ryu,Chung Heon, AU - Park,Soon A, AU - Kim,Seong Muk, AU - Lim,Jung Yeon, AU - Jeong,Chang Hyun, AU - Jun,Jin Ae, AU - Oh,Ji Hyeon, AU - Park,Sun Hwa, AU - Oh,Won-Il, AU - Jeun,Sin-Soo, Y1 - 2010/06/15/ PY - 2010/05/15/received PY - 2010/06/10/accepted PY - 2010/6/19/entrez PY - 2010/6/19/pubmed PY - 2010/8/18/medline SP - 105 EP - 10 JF - Biochemical and biophysical research communications JO - Biochem. Biophys. Res. Commun. VL - 398 IS - 1 N2 - Human mesenchymal stem cells (hMSCs) have been used for cell-based therapies in degenerative disease and as vehicles for delivering therapeutic genes to sites of injury and tumors. Recently, umbilical cord blood (UCB) was identified as a source for MSCs, and human UCB-derived MSCs (hUCB-MSCs) can serve as an alternative source of bone marrow-derived mesenchymal stem cells (BM-MSCs). However, migration signaling pathways required for homing and recruitment of hUCB-MSCs are not fully understood. Stromal cell-derived factor-1 (SDF-1), a ligand for the CXCR4 chemokine receptor, plays a pivotal role in mobilization and homing of stem cells and modulates different biological responses in various stem cells. In this study, expression of CXCR4 in hUCB-MSCs was studied by western blot analysis and the functional role of SDF-1 was assessed. SDF-1 induced the migration of hUCB-MSCs in a dose-dependent manner. The induced migration was inhibited by the CXCR4-specific peptide antagonist (AMD3100) and by inhibitors of phosphoinositide 3-kinase (LY294002), mitogen-activated protein kinase/extracellular signal related kinase (PD98059) and p38MAPK inhibitor (SB203580). hUCB-MSCs treated with SDF-1 displayed increased phosphorylation of Akt, ERK and p38, which were inhibited by AMD3100. Small-interfering RNA-mediated knock-down of Akt, ERK and p38 blocked SDF-1 induced hUCB-MSC migration. In addition, SDF-1-induced actin polymerization was also blocked by these inhibitors. Taken together, these results demonstrate that Akt, ERK and p38 signal transduction pathways may be involved in SDF-1-mediated migration of hUCB-MSCs. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/20558135/Migration_of_human_umbilical_cord_blood_mesenchymal_stem_cells_mediated_by_stromal_cell_derived_factor_1/CXCR4_axis_via_Akt_ERK_and_p38_signal_transduction_pathways_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(10)01153-8 DB - PRIME DP - Unbound Medicine ER -