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Lysophosphatidic Acid Induces Migration of Human Lung‐Resident Mesenchymal Stem Cells Through the β‐Catenin Pathway

dc.contributor.authorBadri, Lindaen_US
dc.contributor.authorLama, Vibha N.en_US
dc.date.accessioned2012-09-05T14:46:09Z
dc.date.available2013-10-18T17:47:29Zen_US
dc.date.issued2012-09en_US
dc.identifier.citationBadri, Linda; Lama, Vibha N. (2012). "Lysophosphatidic Acid Induces Migration of Human Lung‐Resident Mesenchymal Stem Cells Through the β‐Catenin Pathway ." STEM CELLS 30(9): 2010-2019. <http://hdl.handle.net/2027.42/93548>en_US
dc.identifier.issn1066-5099en_US
dc.identifier.issn1549-4918en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/93548
dc.description.abstractMesenchymal stem cells (MSCs) have been demonstrated to reside in human adult organs. However, mechanisms of migration of these endogenous MSCs within their tissue of origin are not well understood. Here, we investigate migration of human adult lung‐resident (LR) mesenchymal progenitor cells. We demonstrate that bioactive lipid lysophosphatidic acid (LPA) plays a principal role in the migration of human LR‐MSCs through a signaling pathway involving LPA1‐induced β‐catenin activation. LR‐MSCs isolated from human lung allografts and lungs of patients with scleroderma demonstrated a robust migratory response to LPA in vitro. Furthermore, LPA levels correlated with LR‐MSC numbers in bronchoalveolar lavage (BAL), providing demonstration of the in vivo activity of LPA in human adult lungs. Migration of LR‐MSCs was mediated via LPA1 receptor ligation and LPA1 silencing significantly abrogated the migratory response of LR‐MSCs to LPA as well as human BAL. LPA treatment of LR‐MSCs induced protein kinase C‐mediated glycogen synthase kinase‐3β phosphorylation, with resulting cytoplasmic accumulation and nuclear translocation of β‐catenin. TCF/LEF dual luciferase gene reporter assay demonstrated a significant increase in transcriptional activity after LPA treatment. LR‐MSC migration and increase in reporter gene activity in the presence of LPA were abolished by transfection with β‐catenin small interfering RNA demonstrating that β‐catenin is critical in mediating LPA‐induced LR‐MSC migration. These data delineate a novel signaling pathway through which ligation of a G protein‐coupled receptor by a biologically relevant lipid mediator induces migration of human tissue‐resident mesenchymal progenitors. S tem C ells 2012;30:2010–2019en_US
dc.publisherWiley Subscription Services, Inc., A Wiley Companyen_US
dc.subject.otherLysophosphatidic Aciden_US
dc.subject.otherβ‐Cateninen_US
dc.subject.otherMesenchymal Stem Cellen_US
dc.subject.otherTissue‐Residenten_US
dc.subject.otherLungen_US
dc.subject.otherMigrationen_US
dc.titleLysophosphatidic Acid Induces Migration of Human Lung‐Resident Mesenchymal Stem Cells Through the β‐Catenin Pathwayen_US
dc.typeArticleen_US
dc.rights.robotsIndexNoFollowen_US
dc.subject.hlbsecondlevelMolecular, Cellular and Developmental Biologyen_US
dc.subject.hlbtoplevelHealth Sciencesen_US
dc.description.peerreviewedPeer Revieweden_US
dc.contributor.affiliationumDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System, 1500 E Medical Center Drive, 3916 Taubman Center, Ann Arbor, Michigan 48109‐0360, USAen_US
dc.contributor.affiliationumDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, Michigan, USAen_US
dc.identifier.pmid22782863en_US
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/93548/1/1171_ftp.pdf
dc.identifier.doi10.1002/stem.1171en_US
dc.identifier.sourceSTEM CELLSen_US
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dc.owningcollnameInterdisciplinary and Peer-Reviewed


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