Understanding abnormal retinoid signaling as a causative mechanism in congenital diaphragmatic hernia

American Journal of Respiratory Cell and Molecular Biology
Robin D ClugstonJohn J Greer

Abstract

Congenital diaphragmatic hernia (CDH) is a frequently occurring source of severe neonatal respiratory distress. It has been hypothesized that abnormal retinoid signaling contributes to the etiology of this developmental anomaly. Here, we use rodent models toward specifically understanding the role of retinoid signaling in the developing diaphragm and how its perturbation is a common mechanism in drug-induced CDH. This includes monitoring of retinoic acid (RA) response element (RARE) activation with RARE-lacZ mice, RA supplementation studies, systematic analyses of the expression profile of key elements in the RA signaling pathway within the developing diaphragm, and the in utero delivery of a RA receptor (RAR) antagonist. These data demonstrate the timing of RARE perturbation by CDH-inducing teratogens and the efficacy of RA supplementation. Furthermore, a detailed profile of retinoid binding proteins, synthetic enzymes, and retinoid receptors within primordial diaphragm cells was obtained. The expression profile of RAR-alpha was particularly striking in regard to its overlap with the regions of primordial diaphragm affected in multiple CDH models. Blocking of RAR signaling with the pan-RAR antagonist BMS493 induced a very high...Continue Reading

References

May 8, 2013·Proceedings of the National Academy of Sciences of the United States of America·Garry L Coles, Kate G Ackerman
Jan 5, 2012·Orphanet Journal of Rare Diseases·J A Tovar
Jan 19, 2012·Nutrients·Margaret Clagett-Dame, Danielle Knutson
Aug 12, 2014·Proceedings of the National Academy of Sciences of the United States of America·Mauro LongoniPatricia K Donahoe
May 10, 2011·Revue des maladies respiratoires·A LabbéP-J Déchelotte
Apr 6, 2011·Seminars in Fetal & Neonatal Medicine·I SluiterD Tibboel
Apr 3, 2012·Pediatric Pulmonology·D C M VeenmaD Tibboel
Apr 17, 2013·The FEBS Journal·Allyson J Merrell, Gabrielle Kardon
May 25, 2012·American Journal of Obstetrics and Gynecology·Augusto F SchmidtLourenço Sbragia
May 15, 2013·Respiratory Physiology & Neurobiology·John J Greer
Feb 22, 2013·Birth Defects Research. Part B, Developmental and Reproductive Toxicology·Jens DingemannPrem Puri
Aug 5, 2017·Disease Models & Mechanisms·Gabrielle KardonWendy K Chung
Jun 16, 2010·Birth Defects Research. Part B, Developmental and Reproductive Toxicology·David E KlingDavid S Newburg
Jul 4, 2019·American Journal of Physiology. Lung Cellular and Molecular Physiology·Heleen M KoolRobbert J Rottier
Aug 16, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·Daphne S MousRobbert J Rottier
May 11, 2018·American Journal of Physiology. Lung Cellular and Molecular Physiology·Daphne S MousRobbert J Rottier
Mar 4, 2011·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Shogo HayashiTakashi Nakano

Citations

Oct 1, 1977·The American Journal of Physiology·Y I TakahashiD S Goodman
Dec 1, 1992·Teratology·C P TorfsL H Honoré
Feb 1, 1994·Mechanisms of Development·Pascal DolléP Chambon
Aug 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·T LufkinP Chambon
Aug 1, 1997·Journal of Applied Physiology·Douglas W Allan, John J Greer
Dec 10, 1997·Mechanisms of Development·D A KleinjanF Grosveld
Jan 20, 1999·Proceedings of the National Academy of Sciences of the United States of America·O WendlingM Mark
Jun 21, 2001·Pediatric Surgery International·J YuJ A Tovar
Oct 6, 2001·American Journal of Respiratory and Critical Care Medicine·B ThébaudJ R Bourbon
Oct 22, 2002·American Journal of Physiology. Lung Cellular and Molecular Physiology·Randal P Babiuk, John J Greer
Jan 1, 2003·The Journal of Comparative Neurology·Randal P BabiukJohn J Greer
Jan 28, 2003·The American Journal of Pathology·Jörg MeyJohn J Greer
Mar 7, 2003·Pediatric Research·John J GreerBernard Thébaud
Jul 2, 2003·Mechanisms of Development·Claire ChazaudRichard Mollard
Jan 20, 2004·American Journal of Physiology. Lung Cellular and Molecular Physiology·Randal P BabiukJohn J Greer
Mar 3, 2006·Birth Defects Research. Part A, Clinical and Molecular Teratology·Wei YangGary M Shaw
Feb 3, 2007·Journal of Pediatric Surgery·Nana NakazawaPrem Puri
Apr 28, 2007·Seminars in Pediatric Surgery·Robin D Clugston, John J Greer
Aug 21, 2007·American Journal of Physiology. Lung Cellular and Molecular Physiology·B Rhiannon NobleJohn J Greer
Feb 12, 2008·American Journal of Physiology. Lung Cellular and Molecular Physiology·Robin D ClugstonJohn J Greer
Mar 1, 2007·Animal : an International Journal of Animal Bioscience·K CosteV Sapin

Related Concepts

Entire Diaphragm
Microphthalmia, Syndromic 6 (Disorder)
Enzymes, antithrombotic
Uterus
Antagonist Muscle Action
Retinal dehydrogenase
Crabp1 protein, mouse
Signal Transduction Pathways
Respiratory Distress Syndrome, Newborn
Etiology

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