Adrenomedullin Deficiency Potentiates Lipopolysaccharide-Induced Experimental Bronchopulmonary Dysplasia in Neonatal Mice.
Journal
The American journal of pathology
ISSN: 1525-2191
Titre abrégé: Am J Pathol
Pays: United States
ID NLM: 0370502
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
received:
19
02
2021
revised:
24
08
2021
accepted:
02
09
2021
pubmed:
12
9
2021
medline:
15
12
2021
entrez:
11
9
2021
Statut:
ppublish
Résumé
Lung inflammation interrupts alveolarization and causes bronchopulmonary dysplasia (BPD). Besides mechanical ventilation and hyperoxia, sepsis contributes to BPD pathogenesis. Adrenomedullin (Adm) is a multifunctional peptide that exerts anti-inflammatory effects in the lungs of adult rodents. Whether Adm mitigates sepsis-induced neonatal lung injury is unknown. The lung phenotype of mice exposed to early postnatal lipopolysaccharide (LPS) was recently shown to be similar to that in human BPD. This model was used to test the hypothesis that Adm-deficient neonatal mice will display increased LPS-induced lung injury than their wild-type (WT) littermates. Adm-deficient mice or their WT littermates were intraperitoneally administered 6 mg/kg of LPS or vehicle daily on postnatal days (PNDs) 3 to 5. The lungs were harvested at several time points to quantify inflammation, alveolarization, and vascularization. The extent of LPS-induced lung inflammation in Adm-deficient mice was 1.6-fold to 10-fold higher than their WT littermates. Strikingly, Adm deficiency induced STAT1 activation and potentiated STAT3 activation in LPS-exposed lungs. The severity of LPS-induced interruption of lung development was also greater in Adm-deficient mice at PND7. At PND14, LPS-exposed WT littermates displayed substantial improvement in lung development, whereas LPS-exposed Adm-deficient mice continued to have decreased lung development. These data indicate that Adm is necessary to decrease lung inflammation and injury and promote repair of the injured lungs in LPS-exposed neonatal mice.
Identifiants
pubmed: 34508690
pii: S0002-9440(21)00385-0
doi: 10.1016/j.ajpath.2021.09.001
pmc: PMC8647431
pii:
doi:
Substances chimiques
Lipopolysaccharides
0
Adrenomedullin
148498-78-6
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2080-2090Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK056338
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL139594
Pays : United States
Informations de copyright
Copyright © 2021 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Références
Am J Pathol. 2020 Mar;190(3):711-722
pubmed: 32093901
Am J Perinatol. 2015 Jan;32(1):43-8
pubmed: 24792766
Nature. 1998 May 28;393(6683):333-9
pubmed: 9620797
Physiol Genomics. 2011 Nov 7;43(21):1226-40
pubmed: 21878612
Am J Physiol Lung Cell Mol Physiol. 2007 Aug;293(2):L446-52
pubmed: 17557801
Pediatrics. 1999 Dec;104(6):1345-50
pubmed: 10585987
J Investig Med. 2014 Jan;62(1):49-55
pubmed: 24169318
J Perinatol. 2016 Dec;36(12):1045-1048
pubmed: 27583395
Am J Respir Crit Care Med. 2019 Oct 15;200(8):1045-1056
pubmed: 31199666
J Am Coll Surg. 2007 Aug;205(2):284-93
pubmed: 17660075
Pediatrics. 2009 May;123(5):1314-9
pubmed: 19403497
Endocrine. 2012 Apr;41(2):256-65
pubmed: 22042486
Am J Physiol Lung Cell Mol Physiol. 2005 Mar;288(3):L536-45
pubmed: 15579624
Am J Physiol Lung Cell Mol Physiol. 2017 Sep 1;313(3):L491-L506
pubmed: 28572154
J Endocrinol. 2004 May;181(2):339-45
pubmed: 15128282
Cardiovasc Res. 2015 Jun 1;106(3):365-74
pubmed: 25784694
Pediatr Res. 1999 Dec;46(6):641-3
pubmed: 10590017
Am J Respir Crit Care Med. 2015 Jul 15;192(2):134-56
pubmed: 26038806
Pediatrics. 2010 Apr;125(4):e736-40
pubmed: 20231184
Mol Biotechnol. 2001 Nov;19(3):279-96
pubmed: 11721624
Ann Am Thorac Soc. 2014 Apr;11 Suppl 3:S146-53
pubmed: 24754823
Sci Rep. 2019 Apr 10;9(1):5863
pubmed: 30971743
Am J Physiol Lung Cell Mol Physiol. 2005 Dec;289(6):L962-70
pubmed: 16024721
Pediatr Res. 1999 Feb;45(2):282-5
pubmed: 10022603
Virulence. 2014 Jan 1;5(1):143-53
pubmed: 24022070
Biomed Res Int. 2013;2013:960101
pubmed: 23984422
Annu Rev Physiol. 2005;67:623-61
pubmed: 15709973
Hum Cell. 2019 Jan;32(1):12-21
pubmed: 30306504
Arch Immunol Ther Exp (Warsz). 2001;49(4):279-83
pubmed: 11726030
J Gastroenterol. 2005 Dec;40(12):1123-9
pubmed: 16378176
Peptides. 2007 Nov;28(11):2164-70
pubmed: 17889965
Am J Physiol Lung Cell Mol Physiol. 2015 Sep 15;309(6):L593-604
pubmed: 26163511
Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):615-9
pubmed: 11149956
Int J Med Microbiol. 2007 Sep;297(5):393-400
pubmed: 17452126
Biochem Biophys Res Commun. 2000 Apr 29;271(1):197-202
pubmed: 10777702
Allergy. 2012 Aug;67(8):998-1006
pubmed: 22686590
Front Med (Lausanne). 2015 Dec 21;2:90
pubmed: 26734611
Int J Chron Obstruct Pulmon Dis. 2016 Jul 14;11:1597-605
pubmed: 27478373
Endocr Rev. 2000 Apr;21(2):138-67
pubmed: 10782362
Microbiol Immunol. 2009 Oct;53(10):573-81
pubmed: 19780971
Am J Respir Crit Care Med. 2007 May 15;175(10):978-85
pubmed: 17272782
Am J Respir Cell Mol Biol. 2016 Dec;55(6):767-778
pubmed: 27438994
J Korean Med Sci. 2015 Oct;30 Suppl 1:S67-74
pubmed: 26566360
Am J Perinatol. 2015 Jun;32(7):675-82
pubmed: 25486288
Am J Physiol Lung Cell Mol Physiol. 2019 Jan 1;316(1):L229-L244
pubmed: 30307313
Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1879-84
pubmed: 12571365
Birth Defects Res A Clin Mol Teratol. 2014 Mar;100(3):145-57
pubmed: 24639412
Am J Physiol Lung Cell Mol Physiol. 2012 Nov 1;303(9):L778-87
pubmed: 22962010
Arch Dis Child Fetal Neonatal Ed. 2006 Mar;91(2):F132-5
pubmed: 16492951
Mediators Inflamm. 2012;2012:717851
pubmed: 22685374
Am J Respir Crit Care Med. 2009 Dec 1;180(11):1122-30
pubmed: 19713447
Am J Respir Crit Care Med. 2005 Sep 1;172(5):581-9
pubmed: 15947283
Am J Perinatol. 2017 Jan;34(1):80-87
pubmed: 27240094
Thorax. 2010 Dec;65(12):1077-84
pubmed: 20971983
Am J Respir Cell Mol Biol. 2010 Aug;43(2):152-60
pubmed: 19738161
Am J Physiol Lung Cell Mol Physiol. 2011 Mar;300(3):L330-40
pubmed: 21239535
Cell Tissue Res. 2002 Oct;310(1):41-50
pubmed: 12242482