title: Deregulation of Retinaldehyde Dehydrogenase 2 Leads to Defective Angiogenic Function of Endothelial Colony-Forming Cells in Pediatric Moyamoya Disease.
abstract: Moyamoya disease (MMD) is a common cause of childhood stroke, in which the abnormal function of the endothelial colony-forming cell (ECFC) plays a key role in the pathogenesis of the disease. This study was designed to identify genes involved in MMD pathogenesis using gene expression profiling and to understand the defective function of MMD ECFCs.
  We compared gene expression profiles of ECFCs isolated from patients with MMD and normal controls. Among the differentially expressed genes, we selected a gene with the most downregulated expression, retinaldehyde dehydrogenase 2 (RALDH2). The activity of RALDH2 in MMD ECFCs was assessed by in vitro tube formation assay and in vivo Matrigel plug assay in the presence of all-trans retinoic acid. The transcriptional control of RALDH2 was tested using ChIP assays on acetyl-histone H3. In the results, MMD ECFCs inefficiently formed capillary tubes in vitro and capillaries in vivo, a defect restored by all-trans retinoic acid treatment. Knockdown of RALDH2 mRNA in normal ECFCs also induced decreased activity of capillary formation in vitro. The decreased level of RALDH2 mRNA in MMD ECFCs was attributed to defective acetyl-histone H3 binding to the promoter region.
  From these results, we conclude that the expression of RALDH2 was epigenetically suppressed in ECFCs from patients with MMD, which may play a key role in their functional impairment.
authors.affiliation: From the Department of Anatomy (J.Y.L.), Division of Pediatric Neurosurgery, Seoul National University Children's Hospital (J.Y.L., Y.J.M., S.-A.C., K.-C.W., J.W.H., J.H.P., S.-K.K.), and Department of Neurosurgery (H.S.K., J.E.K.), Seoul National University College of Medicine, Seoul, Korea; Samsung Genome Institute, Samsung Medical Center, Seoul, Korea (H.-O.L., J.-G.J., W.-Y.P.); College of Pharmacy, Sunchon National University, Jeonnam, Korea (A.-K.P.); and Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea (H.-O.L., W.-Y.P.).
authors.forename: Ji Yeoun
authors.initials: JY
authors.lastname: Lee
authors.affiliation: From the Department of Anatomy (J.Y.L.), Division of Pediatric Neurosurgery, Seoul National University Children's Hospital (J.Y.L., Y.J.M., S.-A.C., K.-C.W., J.W.H., J.H.P., S.-K.K.), and Department of Neurosurgery (H.S.K., J.E.K.), Seoul National University College of Medicine, Seoul, Korea; Samsung Genome Institute, Samsung Medical Center, Seoul, Korea (H.-O.L., J.-G.J., W.-Y.P.); College of Pharmacy, Sunchon National University, Jeonnam, Korea (A.-K.P.); and Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea (H.-O.L., W.-Y.P.).
authors.forename: Youn Joo
authors.initials: YJ
authors.lastname: Moon
authors.affiliation: From the Department of Anatomy (J.Y.L.), Division of Pediatric Neurosurgery, Seoul National University Children's Hospital (J.Y.L., Y.J.M., S.-A.C., K.-C.W., J.W.H., J.H.P., S.-K.K.), and Department of Neurosurgery (H.S.K., J.E.K.), Seoul National University College of Medicine, Seoul, Korea; Samsung Genome Institute, Samsung Medical Center, Seoul, Korea (H.-O.L., J.-G.J., W.-Y.P.); College of Pharmacy, Sunchon National University, Jeonnam, Korea (A.-K.P.); and Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea (H.-O.L., W.-Y.P.).
authors.forename: Hae-Ock
authors.initials: HO
authors.lastname: Lee
authors.affiliation: From the Department of Anatomy (J.Y.L.), Division of Pediatric Neurosurgery, Seoul National University Children's Hospital (J.Y.L., Y.J.M., S.-A.C., K.-C.W., J.W.H., J.H.P., S.-K.K.), and Department of Neurosurgery (H.S.K., J.E.K.), Seoul National University College of Medicine, Seoul, Korea; Samsung Genome Institute, Samsung Medical Center, Seoul, Korea (H.-O.L., J.-G.J., W.-Y.P.); College of Pharmacy, Sunchon National University, Jeonnam, Korea (A.-K.P.); and Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea (H.-O.L., W.-Y.P.).
authors.forename: Ae-Kyung
authors.initials: AK
authors.lastname: Park
authors.affiliation: From the Department of Anatomy (J.Y.L.), Division of Pediatric Neurosurgery, Seoul National University Children's Hospital (J.Y.L., Y.J.M., S.-A.C., K.-C.W., J.W.H., J.H.P., S.-K.K.), and Department of Neurosurgery (H.S.K., J.E.K.), Seoul National University College of Medicine, Seoul, Korea; Samsung Genome Institute, Samsung Medical Center, Seoul, Korea (H.-O.L., J.-G.J., W.-Y.P.); College of Pharmacy, Sunchon National University, Jeonnam, Korea (A.-K.P.); and Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea (H.-O.L., W.-Y.P.).
authors.forename: Seung-Ah
authors.initials: SA
authors.lastname: Choi
authors.affiliation: From the Department of Anatomy (J.Y.L.), Division of Pediatric Neurosurgery, Seoul National University Children's Hospital (J.Y.L., Y.J.M., S.-A.C., K.-C.W., J.W.H., J.H.P., S.-K.K.), and Department of Neurosurgery (H.S.K., J.E.K.), Seoul National University College of Medicine, Seoul, Korea; Samsung Genome Institute, Samsung Medical Center, Seoul, Korea (H.-O.L., J.-G.J., W.-Y.P.); College of Pharmacy, Sunchon National University, Jeonnam, Korea (A.-K.P.); and Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea (H.-O.L., W.-Y.P.).
authors.forename: Kyu-Chang
authors.initials: KC
authors.lastname: Wang
authors.affiliation: From the Department of Anatomy (J.Y.L.), Division of Pediatric Neurosurgery, Seoul National University Children's Hospital (J.Y.L., Y.J.M., S.-A.C., K.-C.W., J.W.H., J.H.P., S.-K.K.), and Department of Neurosurgery (H.S.K., J.E.K.), Seoul National University College of Medicine, Seoul, Korea; Samsung Genome Institute, Samsung Medical Center, Seoul, Korea (H.-O.L., J.-G.J., W.-Y.P.); College of Pharmacy, Sunchon National University, Jeonnam, Korea (A.-K.P.); and Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea (H.-O.L., W.-Y.P.).
authors.forename: Jung Woo
authors.initials: JW
authors.lastname: Han
authors.affiliation: From the Department of Anatomy (J.Y.L.), Division of Pediatric Neurosurgery, Seoul National University Children's Hospital (J.Y.L., Y.J.M., S.-A.C., K.-C.W., J.W.H., J.H.P., S.-K.K.), and Department of Neurosurgery (H.S.K., J.E.K.), Seoul National University College of Medicine, Seoul, Korea; Samsung Genome Institute, Samsung Medical Center, Seoul, Korea (H.-O.L., J.-G.J., W.-Y.P.); College of Pharmacy, Sunchon National University, Jeonnam, Korea (A.-K.P.); and Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea (H.-O.L., W.-Y.P.).
authors.forename: Je-Gun
authors.initials: JG
authors.lastname: Joung
authors.affiliation: From the Department of Anatomy (J.Y.L.), Division of Pediatric Neurosurgery, Seoul National University Children's Hospital (J.Y.L., Y.J.M., S.-A.C., K.-C.W., J.W.H., J.H.P., S.-K.K.), and Department of Neurosurgery (H.S.K., J.E.K.), Seoul National University College of Medicine, Seoul, Korea; Samsung Genome Institute, Samsung Medical Center, Seoul, Korea (H.-O.L., J.-G.J., W.-Y.P.); College of Pharmacy, Sunchon National University, Jeonnam, Korea (A.-K.P.); and Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea (H.-O.L., W.-Y.P.).
authors.forename: Hyun Seung
authors.initials: HS
authors.lastname: Kang
authors.affiliation: From the Department of Anatomy (J.Y.L.), Division of Pediatric Neurosurgery, Seoul National University Children's Hospital (J.Y.L., Y.J.M., S.-A.C., K.-C.W., J.W.H., J.H.P., S.-K.K.), and Department of Neurosurgery (H.S.K., J.E.K.), Seoul National University College of Medicine, Seoul, Korea; Samsung Genome Institute, Samsung Medical Center, Seoul, Korea (H.-O.L., J.-G.J., W.-Y.P.); College of Pharmacy, Sunchon National University, Jeonnam, Korea (A.-K.P.); and Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea (H.-O.L., W.-Y.P.).
authors.forename: Jeong Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: From the Department of Anatomy (J.Y.L.), Division of Pediatric Neurosurgery, Seoul National University Children's Hospital (J.Y.L., Y.J.M., S.-A.C., K.-C.W., J.W.H., J.H.P., S.-K.K.), and Department of Neurosurgery (H.S.K., J.E.K.), Seoul National University College of Medicine, Seoul, Korea; Samsung Genome Institute, Samsung Medical Center, Seoul, Korea (H.-O.L., J.-G.J., W.-Y.P.); College of Pharmacy, Sunchon National University, Jeonnam, Korea (A.-K.P.); and Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea (H.-O.L., W.-Y.P.).
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Phi
authors.affiliation: From the Department of Anatomy (J.Y.L.), Division of Pediatric Neurosurgery, Seoul National University Children's Hospital (J.Y.L., Y.J.M., S.-A.C., K.-C.W., J.W.H., J.H.P., S.-K.K.), and Department of Neurosurgery (H.S.K., J.E.K.), Seoul National University College of Medicine, Seoul, Korea; Samsung Genome Institute, Samsung Medical Center, Seoul, Korea (H.-O.L., J.-G.J., W.-Y.P.); College of Pharmacy, Sunchon National University, Jeonnam, Korea (A.-K.P.); and Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea (H.-O.L., W.-Y.P.). woongyang.park@samsung.com nsthomas@snu.ac.kr.
authors.forename: Woong-Yang
authors.initials: WY
authors.lastname: Park
authors.affiliation: From the Department of Anatomy (J.Y.L.), Division of Pediatric Neurosurgery, Seoul National University Children's Hospital (J.Y.L., Y.J.M., S.-A.C., K.-C.W., J.W.H., J.H.P., S.-K.K.), and Department of Neurosurgery (H.S.K., J.E.K.), Seoul National University College of Medicine, Seoul, Korea; Samsung Genome Institute, Samsung Medical Center, Seoul, Korea (H.-O.L., J.-G.J., W.-Y.P.); College of Pharmacy, Sunchon National University, Jeonnam, Korea (A.-K.P.); and Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea (H.-O.L., W.-Y.P.). woongyang.park@samsung.com nsthomas@snu.ac.kr.
authors.forename: Seung-Ki
authors.initials: SK
authors.lastname: Kim
mesh_terms: D000080924:Aldehyde Dehydrogenase 1 Family; D042783:Endothelial Cells / Q000201:enzymology*; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D006801:Humans; D009072:Moyamoya Disease / Q000201:enzymology* / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D050697:Retinal Dehydrogenase / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D014212:Tretinoin; D000080924:Aldehyde Dehydrogenase 1 Family; C545372:ALDH1A2 protein, human; D050697:Retinal Dehydrogenase
keywords: RALDH2 protein; arteries; moyamoya disease