title: Neonatal steroids induce a down-regulation of tenascin-C and elastin and cause a deceleration of the first phase and an acceleration of the second phase of lung alveolarization.
abstract: Pre- and postnatal corticosteroids are often used in perinatal medicine to improve pulmonary function in preterm infants. To mimic this clinical situation, newborn rats were treated systemically with dexamethasone (Dex), 0.1-0.01 mg/kg/day on days P1-P4. We hypothesized that postnatal Dex may have an impact on alveolarization by interfering with extracellular matrix proteins and cellular differentiation. Morphological alterations were observed on 3D images obtained by high-resolution synchrotron radiation X-ray tomographic microscopy. Alveolarization was quantified stereologically by estimating the formation of new septa between days P4 and P60. The parenchymal expression of tenascin-C (TNC), smooth muscle actin (SMA), and elastin was measured by immunofluorescence and gene expression for TNC by qRT-PCR. After Dex treatment, the first phase of alveolarization was significantly delayed between days P6 and P10, whereas the second phase was accelerated. Elastin and SMA expressions were delayed by Dex treatment, whereas TNC expression was delayed and prolonged. A short course of neonatal steroids impairs the first phase of alveolarization, most likely by altering the TNC and elastin expression. Due to an overshooting catch-up during the second phase of alveolarization, the differences disappear when the animals reach adulthood.
authors.affiliation: Clinic of Neonatology, University Hospital and University of Lausanne, Avenue Pierre Decker, 1011, Lausanne, Switzerland, Matthias.roth@chuv.ch.
authors.forename: Matthias
authors.initials: M
authors.lastname: Roth-Kleiner
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Berger
authors.forename: Sandrine
authors.initials: S
authors.lastname: Gremlich
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Tschanz
authors.forename: Sonja I
authors.initials: SI
authors.lastname: Mund
authors.forename: Martin
authors.initials: M
authors.lastname: Post
authors.forename: Marco
authors.initials: M
authors.lastname: Stampanoni
authors.forename: Johannes C
authors.initials: JC
authors.lastname: Schittny
mesh_terms: D000199:Actins / Q000096:biosynthesis; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation; D004549:Elastin / Q000096:biosynthesis*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008297:Male; D023421:Models, Animal; D038081:Organogenesis / Q000187:drug effects*; D011650:Pulmonary Alveoli / Q000196:embryology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019063:Tenascin / Q000096:biosynthesis*
chemical_list: D000199:Actins; D003907:Dexamethasone; D004549:Elastin; D016326:Extracellular Matrix Proteins; D019063:Tenascin; C498862:Acta2 protein, rat
references.citation: Neonatology. 2010;98(4):289-96
references.pmid: 20453523
references.citation: Arch Dis Child Fetal Neonatal Ed. 2007 Sep;92(5):F334-7
references.pmid: 17712183
references.citation: Am J Respir Cell Mol Biol. 2004 Mar;30(3):360-6
references.pmid: 12904321
references.citation: Pediatr Res. 2003 Jan;53(1):72-80
references.pmid: 12508084
references.citation: Am J Physiol Lung Cell Mol Physiol. 2004 Oct;287(4):L715-7
references.pmid: 15355862
references.citation: Pediatrics. 1972 Oct;50(4):515-25
references.pmid: 4561295
references.citation: Am J Physiol. 1995 Oct;269(4 Pt 1):L482-91
references.pmid: 7485520
references.citation: Am J Respir Crit Care Med. 2012 Jan 15;185(2):186-91
references.pmid: 22071328
references.citation: Respir Physiol Neurobiol. 2010 Apr 30;171(2):72-4
references.pmid: 20206304
references.citation: Dev Biol. 1994 Feb;161(2):615-25
references.pmid: 7508872
references.citation: Dev Dyn. 2005 Aug;233(4):1261-71
references.pmid: 15937935
references.citation: J Clin Invest. 1985 Oct;76(4):1297-305
references.pmid: 4056033
references.citation: Biol Neonate. 2006;89(4):313-22
references.pmid: 16770071
references.citation: Am J Physiol Lung Cell Mol Physiol. 2007 Sep;293(3):L570-9
references.pmid: 17586691
references.citation: Biochim Biophys Acta. 2004 Sep 17;1693(3):193-204
references.pmid: 15363633
references.citation: Development. 1997 Oct;124(20):3943-53
references.pmid: 9374392
references.citation: Biol Neonate. 1995;68(4):229-45
references.pmid: 8580214
references.citation: Am J Physiol. 1989 Oct;257(4 Pt 1):L240-7
references.pmid: 2801952
references.citation: J Synchrotron Radiat. 2010 Sep;17(5):590-9
references.pmid: 20724780
references.citation: Am J Respir Cell Mol Biol. 2000 Jul;23(1):11-8
references.pmid: 10873148
references.citation: Am J Physiol. 1986 Aug;251(2 Pt 2):R218-24
references.pmid: 3740302
references.citation: Biol Neonate. 2003;83(1):57-64
references.pmid: 12566685
references.citation: J Perinatol. 2002 Mar;22(2):101-7
references.pmid: 11896513
references.citation: Eur Cell Mater. 2004 Apr 16;7:35-41; discussion 41
references.pmid: 15095254
references.citation: Dev Dyn. 2008 Aug;237(8):2108-16
references.pmid: 18651668
references.citation: Arch Dis Child Fetal Neonatal Ed. 2011 May;96(3):F158-9
references.pmid: 21289014
references.citation: Am J Respir Cell Mol Biol. 1997 Sep;17(3):334-43
references.pmid: 9308920
references.citation: Dev Dyn. 2002 Jan;223(1):155-62
references.pmid: 11803579
references.citation: Treat Respir Med. 2004;3(5):295-306
references.pmid: 15606220
references.citation: Mikroskopie. 1970 Jun;26(1):57-60
references.pmid: 5530651
references.citation: Am J Respir Cell Mol Biol. 2001 Sep;25(3):341-6
references.pmid: 11588012
references.citation: J Biol Chem. 1999 Jul 30;274(31):21840-6
references.pmid: 10419501
references.citation: Paediatr Respir Rev. 2004;5 Suppl A:S321-7
references.pmid: 14980290
references.citation: Pediatr Pulmonol. 2012 Dec;47(12):1204-14
references.pmid: 22782699
references.citation: Pediatr Res. 2002 Feb;51(2):169-76
references.pmid: 11809910
references.citation: Cell. 1996 Jun 14;85(6):863-73
references.pmid: 8681381
references.citation: Eur J Cell Biol. 1992 Oct;59(1):37-46
references.pmid: 1468446
references.citation: Am J Respir Cell Mol Biol. 1998 Jun;18(6):786-93
references.pmid: 9618383
references.citation: Am J Physiol Lung Cell Mol Physiol. 2008 Feb;294(2):L246-54
references.pmid: 18032698
references.citation: Clin Exp Allergy. 2009 May;39(5):688-99
references.pmid: 19309351
references.citation: Histochem Cell Biol. 1995 Apr;103(4):271-9
references.pmid: 7648402