title: Overexpression of FABP3 inhibits human bone marrow derived mesenchymal stem cell proliferation but enhances their survival in hypoxia.
abstract: Studying the proliferative ability of human bone marrow derived mesenchymal stem cells in hypoxic conditions can help us achieve the effective regeneration of ischemic injured myocardium. Cardiac-type fatty acid binding protein (FABP3) is a specific biomarker of muscle and heart tissue injury. This protein is purported to be involved in early myocardial development, adult myocardial tissue repair and responsible for the modulation of cell growth and proliferation. We have investigated the role of FABP3 in human bone marrow derived mesenchymal stem cells under ischemic conditions. MSCs from 12 donors were cultured either in standard normoxic or modified hypoxic conditions, and the differential expression of FABP3 was tested by quantitative (RT)PCR and western blot. We also established stable FABP3 expression in MSCs and searched for variation in cellular proliferation and differentiation bioprocesses affected by hypoxic conditions. We identified: (1) the FABP3 differential expression pattern in the MSCs under hypoxic conditions; (2) over-expression of FABP3 inhibited the growth and proliferation of the MSCs; however, improved their survival in low oxygen environments; (3) the cell growth factors and positive cell cycle regulation genes, such as PCNA, APC, CCNB1, CCNB2 and CDC6 were all down-regulated; while the key negative cell cycle regulation genes TP53, BRCA1, CASP3 and CDKN1A were significantly up-regulated in the cells with FABP3 overexpression. Our data suggested that FABP3 was up-regulated under hypoxia; also negatively regulated the cell metabolic process and the mitotic cell cycle. Overexpression of FABP3 inhibited cell growth and proliferation via negative regulation of the cell cycle and down-regulation of cell growth factors, but enhances cell survival in hypoxic or ischemic conditions.
authors.affiliation: Cellular Biology Section, Cardiothoracic Surgery Research Program, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: wangs3@mail.nih.gov.
authors.forename: Suna
authors.initials: S
authors.lastname: Wang
authors.affiliation: Cellular Biology Section, Cardiothoracic Surgery Research Program, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Yifu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Cellular Biology Section, Cardiothoracic Surgery Research Program, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Oleg
authors.initials: O
authors.lastname: Andreyev
authors.affiliation: Cellular Biology Section, Cardiothoracic Surgery Research Program, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Hoyt
authors.affiliation: Cellular Biology Section, Cardiothoracic Surgery Research Program, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Avneesh
authors.initials: A
authors.lastname: Singh
authors.affiliation: Cellular Biology Section, Cardiothoracic Surgery Research Program, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Hunt
authors.affiliation: Cellular Biology Section, Cardiothoracic Surgery Research Program, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Horvath
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation; D015687:Cell Hypoxia / Q000502:physiology*; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology*; D002478:Cells, Cultured; D015536:Down-Regulation; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006367:HeLa Cells; D006335:Heart Injuries / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000378:metabolism; D007511:Ischemia / Q000235:genetics / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis; D055815:Young Adult
chemical_list: D015415:Biomarkers; C493408:FABP3 protein, human; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger
keywords: Cell cycle; Cell proliferation; FABP3; Human mesenchymal stem cell; Hypoxia