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  • Article
    miR‐9‐5p suppresses pro‐fibrogenic transformation of fibroblasts and prevents organ fibrosis by targeting NOX4 and TGFBR2
    miR‐9‐5p suppresses pro‐fibrogenic transformation of fibroblasts and prevents organ fibrosis by targeting NOX4 and TGFBR2
    1. Marta Fierro‐Fernández1,
    2. Óscar Busnadiego1,
    3. Pilar Sandoval1,
    4. Cristina Espinosa‐Díez1,
    5. Eva Blanco‐Ruiz1,
    6. Macarena Rodríguez2,
    7. Héctor Pian2,
    8. Ricardo Ramos3,
    9. Manuel López‐Cabrera1,
    10. Maria Laura García‐Bermejo2 and
    11. Santiago Lamas*,1
    1. 1Department of Cell Biology and Immunology, Centro de Biología Molecular “Severo Ochoa” (CBMSO), Consejo Superior de Investigaciones Científicas–Universidad Autónoma de Madrid, Madrid, Spain
    2. 2Department of Pathology, Hospital Universitario “Ramón y Cajal”, IRYCIS, Madrid, Spain
    3. 3Genomic Facility, Parque Científico de Madrid, Madrid, Spain
    1. *Corresponding author. Tel: +34 911964455; Fax: +34 911964420; E‐mail: slamas{at}cbm.csic.es

    miR‐9‐5p is discovered as an anti‐fibrotic miRNA that targets TGBR2 and NOX4 to inhibit the transformation of fibroblasts into myofibroblasts. TGF‐β1 itself is pro‐fibrogenic, but promotes miR‐9‐5p expression, thus inducing inhibition of its own pro‐fibrogenic role.

    Synopsis

    miR‐9‐5p is discovered as an anti‐fibrotic miRNA that targets TGBR2 and NOX4 to inhibit the transformation of fibroblasts into myofibroblasts. TGF‐β1 itself is pro‐fibrogenic, but promotes miR‐9‐5p expression, thus inducing inhibition of its own pro‐fibrogenic role.

    • Reactive oxygen species and TGF‐β1 induce miR‐9‐5p expression.

    • miR‐9‐5p inhibits TGFBR2 and NOX4 expression by binding to their 3′‐UTRs.

    • miR‐9‐5p inhibits TGF‐β‐mediated pro‐fibrogenic signaling in human lung fibroblasts and attenuates the development of experimental pulmonary fibrosis.

    • Peritoneal mesothelial fibrogenesis is also significantly reduced by miR‐9‐5p.

    • fibrosis
    • miRNAs
    • myofibroblast
    • oxidative stress
    • TGF‐β signaling
    • Received May 28, 2015.
    • Revision received July 17, 2015.
    • Accepted July 20, 2015.
    Marta Fierro‐Fernández, Óscar Busnadiego, Pilar Sandoval, Cristina Espinosa‐Díez, Eva Blanco‐Ruiz, Macarena Rodríguez, Héctor Pian, Ricardo Ramos, Manuel López‐Cabrera, Maria Laura García‐Bermejo, Santiago Lamas
  • Article
    MicroRNA‐455 regulates brown adipogenesis via a novel HIF1an‐AMPK‐PGC1α signaling network
    MicroRNA‐455 regulates brown adipogenesis via a novel HIF1an‐AMPK‐PGC1α signaling network
    1. Hongbin Zhang*,1,2,
    2. Meiping Guan1,3,
    3. Kristy L Townsend1,
    4. Tian Lian Huang1,
    5. Ding An1,
    6. Xu Yan1,
    7. Ruidan Xue1,
    8. Tim J Schulz1,4,
    9. Jonathon Winnay1,
    10. Marcelo Mori1,5,
    11. Michael F Hirshman1,
    12. Karsten Kristiansen6,
    13. John S Tsang7,
    14. Andrew P White8,
    15. Aaron M Cypess1,
    16. Laurie J Goodyear1 and
    17. Yu‐Hua Tseng*,1,9
    1. 1Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
    2. 2Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
    3. 3Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
    4. 4Adipocyte Development Research Group, German Institute of Human Nutrition, Potsdam, Germany
    5. 5Department of Biophysics, Federal University of Sao Paulo, Sao Paulo, Brazil
    6. 6Department of Biology, University of Copenhagen, Copenhagen, Denmark
    7. 7Systems Genomics and Bioinformatics Unit, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases (NIAID) and Trans‐NIH Center for Human Immunology, National Institutes of Health, Bethesda, MD, USA
    8. 8Department of Orthopaedic Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
    9. 9Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA
    1. * Corresponding author. Tel: +1 45 3533 0484; E‐mail: hongbin{at}sund.ku.dk

      Corresponding author. Tel: +1 617 309 1967; Fax: +1 617 309 2650; E‐mail: yu-hua.tseng{at}joslin.harvard.edu

    miR‐455 promotes brown adipocyte differentiation and thermogenesis by targeting the key adipogenic inhibitors Necdin and Runx1t1 and by inducing a HIF1an‐AMPK‐PGC1α signaling cascade stimulating mitochondria biogenesis.

    Synopsis

    miR‐455 promotes brown adipocyte differentiation and thermogenesis by targeting the key adipogenic inhibitors Necdin and Runx1t1 and by inducing a HIF1an‐AMPK‐PGC1α signaling cascade stimulating mitochondria biogenesis.

    • miR‐455 is expressed in brown adipose tissue and induced by cold.

    • Fat‐specific miR‐455 transgenic mice show browning of subcutaneous white fat upon cold exposure.

    • miR‐455 induces brown/beige adipogenesis by targeting key brown adipogenic inhibitors such as Runx1t1 and Necdin.

    • miR‐455 activates a HIF1an‐AMPK‐PGC1α signaling cascade that promotes thermogenesis.

    • brown adipogenesis
    • differentiation
    • metabolism
    • microRNA
    • UCP1
    • Received June 11, 2015.
    • Revision received July 19, 2015.
    • Accepted July 24, 2015.
    Hongbin Zhang, Meiping Guan, Kristy L Townsend, Tian Lian Huang, Ding An, Xu Yan, Ruidan Xue, Tim J Schulz, Jonathon Winnay, Marcelo Mori, Michael F Hirshman, Karsten Kristiansen, John S Tsang, Andrew P White, Aaron M Cypess, Laurie J Goodyear, Yu‐Hua Tseng
  • Scientific Report
    UTX inhibits EMT‐induced breast CSC properties by epigenetic repression of EMT genes in cooperation with LSD1 and HDAC1
    UTX inhibits EMT‐induced breast CSC properties by epigenetic repression of EMT genes in cooperation with LSD1 and HDAC1
    1. Hee‐Joo Choi1,,
    2. Ji‐Hye Park2,,
    3. Mikyung Park3,
    4. Hee‐Young Won1,
    5. Hyeong‐seok Joo1,
    6. Chang Hoon Lee3,
    7. Jeong‐Yeon Lee*,2 and
    8. Gu Kong*,1,2
    1. 1Department of Pathology, College of Medicine, Hanyang University, Seoul, Korea
    2. 2Institute for Bioengineering and Biopharmaceutical Research (IBBR), Hanyang University, Seoul, Korea
    3. 3College of Pharmacy, Dongguk University, Seoul, Korea
    1. * Corresponding author. Tel: +82 2 2220 0634; Fax: +82 2 2295 1091; E‐mail: jy2jy2{at}hanyang.ac.kr

      Corresponding author. Tel: +82 2 2290 8251; Fax: +82 2 2295 1091; E‐mail: gkong{at}hanyang.ac.kr

    1. These authors contributed equally to this work

    UTX, a histone H3K27 demethylase, epigenetically silences EMT genes by facilitating LSD1‐dependent H3K4 demethylation and HDAC‐dependent histone deacetylation to inhibit EMT‐induced breast CSC properties.

    Synopsis

    UTX, a histone H3K27 demethylase, epigenetically silences EMT genes by facilitating LSD1‐dependent H3K4 demethylation and HDAC‐dependent histone deacetylation to inhibit EMT‐induced breast CSC properties.

    • UTX suppresses EMT and CSC properties in breast cancer.

    • UTX cooperates with LSD1 and HDAC1 to form a transcriptional repressive complex on EMT‐TF promoters.

    • breast CSC
    • EMT
    • UTX
    • Received February 13, 2015.
    • Revision received July 10, 2015.
    • Accepted July 14, 2015.
    Hee‐Joo Choi, Ji‐Hye Park, Mikyung Park, Hee‐Young Won, Hyeong‐seok Joo, Chang Hoon Lee, Jeong‐Yeon Lee, Gu Kong
  • Review
    Ins and outs of GPCR signaling in primary cilia
    Ins and outs of GPCR signaling in primary cilia
    1. Kenneth Bødtker Schou1,
    2. Lotte Bang Pedersen1 and
    3. Søren Tvorup Christensen*,1
    1. 1Department of Biology, University of Copenhagen, Copenhagen, Denmark
    1. *Corresponding author. Tel: +45 51322997; E‐mail: stchristensen{at}bio.ku.dk

    GPCRs are involved in multiple signaling pathways in primary cilia. This article describes how GPCRs traffic into and out of the cilium and how they control ciliary and cellular functions. GPCR‐targeted drug strategies for the treatment of ciliopathies are also discussed.

    • ciliopathies
    • G protein‐coupled receptors
    • intraflagellar transport
    • neuronal signaling
    • primary cilia
    • Received April 10, 2015.
    • Revision received June 24, 2015.
    • Accepted July 1, 2015.
    Kenneth Bødtker Schou, Lotte Bang Pedersen, Søren Tvorup Christensen
  • Correspondence
    Response to Luca L Fava and colleagues
    Response to Luca L Fava and colleagues
    1. Stéphane Frémont1,
    2. Annabelle Gérard1,
    3. Marie Galloux2,
    4. Katy Janvier1,
    5. Roger E Karess3 and
    6. Clarisse Berlioz‐Torrent (clarisse.berlioz{at}inserm.fr)1
    1. 1Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris Descartes, Paris, France
    2. 2Unité de Virologie et Immunologie Moléculaires, INRA, Jouy‐en‐Josas, France
    3. 3Institut Jacques Monod, CNRS, UMR 7592, Université Paris Diderot, Paris, France

    The original authors' response.

    Stéphane Frémont, Annabelle Gérard, Marie Galloux, Katy Janvier, Roger E Karess, Clarisse Berlioz‐Torrent
  • Correspondence
    Beclin 1 is dispensable for chromosome congression and proper outer kinetochore assembly
    Beclin 1 is dispensable for chromosome congression and proper outer kinetochore assembly
    1. Luca L Fava (luca.fava{at}i-med.ac.at)1,
    2. Johannes Rainer23,
    3. Manuel D Haschka1,
    4. Stephan Geley2 and
    5. Andreas Villunger1
    1. 1Division of Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria
    2. 2Division of Molecular Pathophysiology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria
    3. 3Center for Biomedicine, EURAC Research, Bolzano, Italy

    This is a correspondence about “Beclin‐1 is required for chromosome congression and proper outer kinetochore assembly”.

    Luca L Fava, Johannes Rainer, Manuel D Haschka, Stephan Geley, Andreas Villunger
  • Scientific Report
    Glucagon signalling in the dorsal vagal complex is sufficient and necessary for high‐protein feeding to regulate glucose homeostasis in vivo
    <div xmlns="http://www.w3.org/1999/xhtml">Glucagon signalling in the dorsal vagal complex is sufficient and necessary for high‐protein feeding to regulate glucose homeostasis <em>in vivo</em></div>
    1. Mary P LaPierre1,2,
    2. Mona A Abraham1,2,
    3. Jessica TY Yue15,
    4. Beatrice M Filippi1 and
    5. Tony KT Lam*,1,2,3,4
    1. 1Toronto General Research Institute & Department of Medicine UHN, Toronto, Canada
    2. 2Department of Physiology, University of Toronto, Toronto Canada
    3. 3Department of Medicine, University of Toronto, Toronto Canada
    4. 4Banting and Best Diabetes Centre, University of Toronto, Toronto, Canada
    5. 5Department of Physiology, University of Alberta, Edmonton, Canada
    1. *Corresponding author. Tel: +1 416 581 7880; Fax: +1 416 581 7880; E‐mail: tony.lam{at}uhnres.utoronto.ca

    This study introduces a physiological role for brain glucagon action in regulating postprandial glucose homeostasis. Glucagon acts in the DVC to suppress glucose production and to mediate the lowering of plasma glucose after high‐protein feeding.

    Synopsis

    This study introduces a physiological role for brain glucagon action in regulating postprandial glucose homeostasis. Glucagon acts in the DVC to suppress glucose production and to mediate the lowering of plasma glucose after high‐protein feeding.

    • Intra‐DVC administration of glucagon suppresses glucose production in vivo.

    • Glucagon activates a Gcgr–PKA–Erk1/2–KATP channel signalling cascade in the DVC.

    • Disruption of Gcgr signalling in the DVC blunts the ability of high‐protein feeding to acutely lower plasma glucose levels compared to low‐protein feeding.

    • brain
    • glucagon
    • glucose homeostasis
    • protein‐feeding
    • Received April 2, 2015.
    • Revision received July 22, 2015.
    • Accepted July 23, 2015.
    Mary P LaPierre, Mona A Abraham, Jessica TY Yue, Beatrice M Filippi, Tony KT Lam