title: Administration of antenatal glucocorticoids and postnatal surfactant ameliorates respiratory distress syndrome-associated neonatal lethality in Erk3(-/-) mouse pups.
abstract: BACKGROUND
  Respiratory distress syndrome (RDS) persists as a prevalent cause of infant morbidity and mortality. We have previously demonstrated that deletion of Erk3 results in pulmonary immaturity and neonatal lethality. Using RNA sequencing, we identified corticotrophin releasing hormone (CRH) and surfactant protein B (SFTPB) as potential molecular mediators of Erk3-dependent lung maturation. In this study, we characterized the impact of antenatal glucocorticoids and postnatal surfactant on neonatal survival of Erk3 null mice.
  
  
  METHODS
  In a double crossover design, we administered dexamethasone (dex) or saline to pregnant dams during the saccular stage of lung development, followed by postnatal surfactant or saline via inhalation intubation. Survival was recorded, and detailed lung histological analysis and staining for CRH and SFTPB protein expression were performed.
  
  
  RESULTS
  Without treatment, Erk3 null pups die within 6 h of birth with reduced aerated space, impaired thinning of the alveolar septa, and abundant glycogen stores, as described in human RDS. The administration of dex and surfactant improved RDS-associated lethality of Erk3(-/-) pups and partially restored functional fetal lung maturation by accelerating the downregulation of pulmonary CRH and partially rescuing the production of SFTPB.
  
  
  CONCLUSIONS
  These findings emphasize that Erk3 is integral to terminal differentiation of type II cells, SFTPB production, and fetal pulmonary maturity.
authors.affiliation: Division of Neonatology, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas.
authors.forename: Milenka
authors.initials: M
authors.lastname: Cuevas Guaman
authors.affiliation: Department of Pathology, University of Texas Medical Branch-Galveston, Galveston, Texas.
authors.forename: Elena
authors.initials: E
authors.lastname: Sbrana
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Shope
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas.
authors.forename: Lori
authors.initials: L
authors.lastname: Showalter
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas.
authors.forename: Min
authors.initials: M
authors.lastname: Hu
authors.affiliation: Institut de Recherche en Immunologie et Cancérologie, Université de Montreal, Montréal, Québec, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Meloche
authors.affiliation: 1] Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas [2] Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, Texas.
authors.forename: Kjersti
authors.initials: K
authors.lastname: Aagaard
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D018592:Cross-Over Studies; D003907:Dexamethasone / Q000008:administration & dosage / Q000737:chemistry; D004195:Disease Models, Animal; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000737:chemistry; D008168:Lung / Q000196:embryology* / Q000254:growth & development* / Q000473:pathology; D008297:Male; D018811:Maternal Exposure; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D048053:Mitogen-Activated Protein Kinase 6 / Q000235:genetics; D011247:Pregnancy; D011270:Pregnancy, Animal; D037701:Pulmonary Surfactant-Associated Protein B / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000008:administration & dosage*; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy* / Q000235:genetics; D013997:Time Factors
chemical_list: D005938:Glucocorticoids; D037701:Pulmonary Surfactant-Associated Protein B; D011663:Pulmonary Surfactants; D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone; C474633:Mapk6 protein, mouse; D048053:Mitogen-Activated Protein Kinase 6
references.citation: J Biol Chem. 2006 Nov 17;281(46):35499-510
references.pmid: 16971392
references.citation: Proc Natl Acad Sci U S A. 2009 Sep 29;106(39):16710-5
references.pmid: 19805361
references.citation: EMBO J. 2004 Dec 8;23(24):4770-9
references.pmid: 15538386
references.citation: Semin Neonatol. 2001 Aug;6(4):331-42
references.pmid: 11972434
references.citation: J Immunol. 2001 May 15;166(10):6376-82
references.pmid: 11342662
references.citation: Front Cell Infect Microbiol. 2012 Dec 20;2:164
references.pmid: 23267442
references.citation: Biochim Biophys Acta. 2007 Aug;1773(8):1376-87
references.pmid: 17161475
references.citation: Am J Respir Crit Care Med. 2010 Feb 15;181(4):394-418
references.pmid: 20130146
references.citation: J Soc Gynecol Investig. 1999 May-Jun;6(3):109-19
references.pmid: 10376266
references.citation: Endocr Rev. 2010 Dec;31(6):783-816
references.pmid: 20631004
references.citation: Am J Obstet Gynecol. 1988 Oct;159(4):891-5
references.pmid: 3263045
references.citation: J Clin Invest. 1994 May;93(5):2066-72
references.pmid: 8182138
references.citation: Biochem J. 2000 Feb 15;346 Pt 1:169-75
references.pmid: 10657254
references.citation: J Appl Physiol (1985). 2007 Jan;102(1):459-67
references.pmid: 16973815
references.citation: Endocr Rev. 2001 Apr;22(2):153-83
references.pmid: 11294822
references.citation: PLoS One. 2012;7(8):e42419
references.pmid: 22879974
references.citation: Nature. 1995 Feb 2;373(6513):427-32
references.pmid: 7830793
references.citation: Am J Physiol Lung Cell Mol Physiol. 2004 Oct;287(4):L743-51
references.pmid: 15169678
references.citation: Toxicol Sci. 2000 May;55(1):24-35
references.pmid: 10788556
references.citation: J Biol Chem. 2003 Oct 24;278(43):42615-24
references.pmid: 12915405
references.citation: Am J Physiol Lung Cell Mol Physiol. 2003 May;284(5):L783-90
references.pmid: 12533442
references.citation: Nat Med. 2002 Jul;8(7):702-10
references.pmid: 12053176
references.citation: Front Biosci. 2007 Jan 01;12:912-8
references.pmid: 17127348
references.citation: Reproduction. 2001 Apr;121(4):493-501
references.pmid: 11277868
references.citation: Treat Respir Med. 2004;3(5):295-306
references.pmid: 15606220
references.citation: Mol Cell Biol. 2011 Mar;31(5):1054-65
references.pmid: 21189286
references.citation: Am J Respir Cell Mol Biol. 2009 Sep;41(3):367-75
references.pmid: 19168701
references.citation: Lab Anim. 1989 Jul;23(3):234-40
references.pmid: 2527323
references.citation: Obstet Gynecol. 2003 Mar;101(3):557-64
references.pmid: 12636962
references.citation: Anat Embryol (Berl). 2006 Mar;211(2):139-53
references.pmid: 16374608
references.citation: Lab Anim. 1982 Apr;16(2):143-5
references.pmid: 7078061
references.citation: Eur J Pharmacol. 2007 Jul 30;568(1-3):1-15
references.pmid: 17543939
references.citation: Anesth Analg. 2004 May;98(5):1273-9, table of contents
references.pmid: 15105199
references.citation: J Reprod Immunol. 1998 Aug;39(1-2):215-20
references.pmid: 9786463
references.citation: Am J Physiol Lung Cell Mol Physiol. 2005 Feb;288(2):L379-83
references.pmid: 15501950
references.citation: Pediatr Pulmonol. 2001 Jul;32(1):76-91
references.pmid: 11416880
references.citation: Eur Respir J. 2010 Mar;35(3):477-8
references.pmid: 20190328
references.citation: Am J Physiol Lung Cell Mol Physiol. 2001 Apr;280(4):L689-94
references.pmid: 11238009
references.citation: Arch Virol. 1999;144(4):675-85
references.pmid: 10365160