title: Oleic acid enhances the motility of umbilical cord blood derived mesenchymal stem cells through EphB2-dependent F-actin formation.
abstract: The role of unsaturated fatty acids (UFAs) is essential for determining stem cell functions. Eph/Ephrin interactions are important for regulation of stem cell fate and localization within their niche, which is significant for a wide range of stem cell behavior. Although oleic acid (OA) and Ephrin receptors (Ephs) have critical roles in the maintenance of stem cell functions, interrelation between Ephs and OA has not been explored. Therefore, the present study investigated the effect of OA-pretreated UCB-MSCs in skin wound-healing and underlying mechanism of Eph expression. OA promoted the motility of UCB-MSCs via EphB2 expression. OA-mediated GPR40 activation leads to Gαq-dependent PKCα phosphorylation. In addition, OA-induced phosphorylation of GSK3β was followed by β-catenin nuclear translocation in UCB-MSCs. Activation of β-catenin was blocked by PKC inhibitors, and OA-induced EphB2 expression was suppressed by β-cateninsiRNA transfection. Of those Rho-GTPases, Rac1 was activated in an EphB2-dependent manner. Accordingly, knocking down EphB2 suppressed F-actin expression. In vivo skin wound-healing assay revealed that OA-treated UCB-MSCs enhanced skin wound repair compared to UCB-MSCs pretreated with EphB2siRNA and OA. In conclusion, we showed that OA enhances UCB-MSC motility through EphB2-dependent F-actin formation involving PKCα/GSK3β/β-catenin and Rac1 signaling pathways.
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine, Research Institute for Veterinary Science, Seoul National University, Seoul 151-741, South Korea; BK21 PLUS Creative Veterinary Research Center, Seoul National University, Seoul 151-741, South Korea.
authors.forename: Young Hyun
authors.initials: YH
authors.lastname: Jung
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine, Research Institute for Veterinary Science, Seoul National University, Seoul 151-741, South Korea; BK21 PLUS Creative Veterinary Research Center, Seoul National University, Seoul 151-741, South Korea.
authors.forename: Sei-Jung
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine, Research Institute for Veterinary Science, Seoul National University, Seoul 151-741, South Korea; BK21 PLUS Creative Veterinary Research Center, Seoul National University, Seoul 151-741, South Korea.
authors.forename: Sang Yub
authors.initials: SY
authors.lastname: Oh
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine, Research Institute for Veterinary Science, Seoul National University, Seoul 151-741, South Korea; BK21 PLUS Creative Veterinary Research Center, Seoul National University, Seoul 151-741, South Korea.
authors.forename: Hyun Jik
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine, Research Institute for Veterinary Science, Seoul National University, Seoul 151-741, South Korea; BK21 PLUS Creative Veterinary Research Center, Seoul National University, Seoul 151-741, South Korea.
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Ryu
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine, Research Institute for Veterinary Science, Seoul National University, Seoul 151-741, South Korea; BK21 PLUS Creative Veterinary Research Center, Seoul National University, Seoul 151-741, South Korea. Electronic address: hjhan@snu.ac.kr.
authors.forename: Ho Jae
authors.initials: HJ
authors.lastname: Han
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D019301:Oleic Acid / Q000494:pharmacology*; D036183:Receptor, EphB2 / Q000502:physiology*; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000199:Actins; D019301:Oleic Acid; D036183:Receptor, EphB2
keywords: Ephrin; Mesenchymal stem cell transplantation; Migration; Oleic acid; Wound healing