PMID- 27161651 OWN - NLM STAT- MEDLINE DCOM- 20170911 LR - 20181202 IS - 1440-1681 (Electronic) IS - 0305-1870 (Linking) VI - 43 IP - 8 DP - 2016 Aug TI - Cytoprotective effects of endothelin-1 on mesenchymal stem cells: an in vitro study. PG - 769-76 LID - 10.1111/1440-1681.12590 [doi] AB - Stem cell-based therapies is a promising approach for regenerative therapy in various diseases. Some obstacles remain to be solved before clinical application of the cell therapy is realized, including increasing the survival of transplanted stem cells, reducing loss of transplanted cells, and maintaining adequate vascular supply. Recently, stem cell preconditioning with chemical and pharmacological agents has been shown to increase therapeutic efficacy. The present study investigated the effect of endothelin-1 (ET-1) on survival, angiogenesis, and migration of mesenchymal stem cells (MSCs), in vitro. MSCs were treated with various concentrations of ET-1 and the expression of cyclooxygenase-2 (COX-2), hypoxia-inducible factor-1 (HIF-1), C-X-C chemokine receptor type 4 (CXCR4), C-C chemokine receptor type 2 (CCR2), vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2), angiopoietin-4 (Ang-4) and matrix metalloproteinase-2 (MMP-2) were examined. Caspase 3 activity and prostaglandin E2 (PGE2) were determined by ELISA assay. MSCs migration and tube formation potential were assessed using scratch test and three dimensional vessel formation assay. ET-1 enhanced the MSCs viability. In ET-1- treated MSCs, expression of COX-2, HIF-1, CXCR4, CCR2, VEGF, Ang-2, Ang-4 and MMP-2 were increased compared to control groups. Elevation of all these genes were reversed by celecoxib (50 mumol/L), a selective COX-2 inhibitor. PGE2 generation, MSCs migration and tube formation were enhanced by ET-1 conditioning, whereas caspase-3 activity was reduced in these cells, compared to the control group. The results presented here reveal that preconditioning of MSCs with ET-1 has strong cytoprotective effects through activation of survival signalling molecules and trophic factors. CI - (c) 2016 John Wiley & Sons Australia, Ltd. FAU - Pourjafar, Mona AU - Pourjafar M AD - Research Centre for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. FAU - Saidijam, Massoud AU - Saidijam M AD - Research Centre for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. FAU - Mansouri, Kamran AU - Mansouri K AD - Medical Biology Research Centre, Kermanshah University of Medical Sciences, Kermanshah, Iran. FAU - Malih, Sara AU - Malih S AD - Research Centre for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. FAU - Ranjbar Nejad, Tayebeh AU - Ranjbar Nejad T AD - Research Centre for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. FAU - Shabab, Nooshin AU - Shabab N AD - Research Centre for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. FAU - Najafi, Rezvan AU - Najafi R AD - Research Centre for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. AD - Endometrium and Endometriosis Research Centre, Hamadan University of Medical Sciences, Hamadan, Iran. LA - eng SI - GENBANK/NM_001106526 SI - GENBANK/NM_001287107 SI - GENBANK/NM_017232 SI - GENBANK/NM_021866 SI - GENBANK/NM_022205 SI - GENBANK/NM_024359 SI - GENBANK/NM_031054 SI - GENBANK/NM_134454 SI - GENBANK/NR_046237 PT - Journal Article PL - Australia TA - Clin Exp Pharmacol Physiol JT - Clinical and experimental pharmacology & physiology JID - 0425076 RN - 0 (Endothelin-1) SB - IM MH - Animals MH - Cell Proliferation/drug effects/physiology MH - Cell Survival/*drug effects/physiology MH - Cells, Cultured MH - Cytoprotection/*drug effects/physiology MH - Dose-Response Relationship, Drug MH - Endothelin-1/*pharmacology MH - Human Umbilical Vein Endothelial Cells/drug effects/physiology MH - Humans MH - Male MH - Mesenchymal Stem Cells/*drug effects/physiology MH - Rats MH - Rats, Wistar OTO - NOTNLM OT - cyclooxygenase-2 OT - endothelin-1 OT - mesenchymal stem cells OT - prostaglandin E2 OT - stem cell therapy EDAT- 2016/05/11 06:00 MHDA- 2017/09/12 06:00 CRDT- 2016/05/11 06:00 PHST- 2016/02/10 00:00 [received] PHST- 2016/05/02 00:00 [revised] PHST- 2016/05/04 00:00 [accepted] PHST- 2016/05/11 06:00 [entrez] PHST- 2016/05/11 06:00 [pubmed] PHST- 2017/09/12 06:00 [medline] AID - 10.1111/1440-1681.12590 [doi] PST - ppublish SO - Clin Exp Pharmacol Physiol. 2016 Aug;43(8):769-76. doi: 10.1111/1440-1681.12590.