Complement inhibitor Crry expression in mouse placenta is essential for maintaining normal blood pressure and fetal growth.
Animals
Blood Pressure
/ genetics
Complement Activation
/ genetics
Complement C3
/ metabolism
Complement Inactivating Agents
/ pharmacology
Female
Fetal Development
/ genetics
Gene Expression Regulation
/ genetics
Mice
Mice, Inbred C57BL
Placenta
/ metabolism
Pre-Eclampsia
/ genetics
Pregnancy
RNA, Small Interfering
/ genetics
Receptors, Complement
/ genetics
Receptors, Complement 3b
/ genetics
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
05
05
2020
accepted:
16
07
2020
entrez:
4
8
2020
pubmed:
4
8
2020
medline:
21
10
2020
Statut:
epublish
Résumé
Many circumstantial evidences from human and animal studies suggest that complement cascade dysregulation may play an important role in pregnancy associated complications including preeclampsia. Deletion of rodent specific complement inhibitor gene, Complement Receptor 1-related Gene/Protein y (Crry) produces embryonic lethal phenotype due to complement activation. It is not clear if decreased expression of Crry during pregnancy produces hypertensive phenotype. We downregulated Crry in placenta by injecting inducible lentivialshRNA vectors into uterine horn of pregnant C57BL/6 mice at the time of blastocyst hatching. Placenta specific downregulation of Crry without significant loss of embryos was achieved upon induction of shRNA using an optimal doxycycline dose at mid gestation. Crry downregulation resulted in placental complement deposition. Late-gestation measurements showed that fetal weights were reduced and blood pressure increased in pregnant mice upon downregulation of Crry suggesting a critical role for Crry in fetal growth and blood pressure regulation.
Identifiants
pubmed: 32745140
doi: 10.1371/journal.pone.0236968
pii: PONE-D-20-13261
pmc: PMC7398533
doi:
Substances chimiques
Complement C3
0
Complement Inactivating Agents
0
Cr1l protein, mouse
0
RNA, Small Interfering
0
Receptors, Complement
0
Receptors, Complement 3b
0
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
e0236968Subventions
Organisme : NICHD NIH HHS
ID : R01 HD094347
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL058144
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Exp Brain Res. 1979;37(3):439-57
pubmed: 230067
J Matern Fetal Neonatal Med. 2005 Apr;17(4):239-45
pubmed: 16147832
Genesis. 2009 Jul;47(7):433-9
pubmed: 19444902
Front Immunol. 2017 May 29;8:589
pubmed: 28611769
Mol Immunol. 2015 Sep;67(1):56-70
pubmed: 25802092
Obstet Gynecol. 2019 Jan;133(1):e1-e25
pubmed: 30575675
Obstet Gynecol. 2018 Dec;132(6):1477-1485
pubmed: 30399106
Biotechniques. 2007 Mar;42(3):317-8, 320, 322-5
pubmed: 17390538
Front Immunol. 2014 Jul 09;5:312
pubmed: 25071773
Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):628-33
pubmed: 9892684
Clin Dev Immunol. 2012;2012:484321
pubmed: 22203857
Kidney Int. 2011 Feb;79(3):331-9
pubmed: 20944547
J Immunol. 2008 Aug 15;181(4):2732-40
pubmed: 18684964
J Immunol. 2015 Aug 1;195(3):1129-38
pubmed: 26071558
J Reprod Immunol. 2013 Apr;97(2):211-6
pubmed: 23415845
Am J Reprod Immunol. 1999 May;41(5):343-52
pubmed: 10378030
PLoS One. 2011 Jan 21;6(1):e16348
pubmed: 21283713
Nat Rev Nephrol. 2016 Jul;12(7):383-401
pubmed: 27211870
Am J Reprod Immunol. 2018 Nov;80(5):e13033
pubmed: 30099798
Dis Markers. 2015;2015:263109
pubmed: 26556948
Biochem J. 1998 Feb 15;330 ( Pt 1):163-8
pubmed: 9461505
J Immunol. 1989 Sep 15;143(6):2058-67
pubmed: 2528587
Immunity. 2003 Dec;19(6):813-22
pubmed: 14670299
Semin Nephrol. 2013 Nov;33(6):479-92
pubmed: 24161035
J Exp Med. 1992 Jan 1;175(1):121-9
pubmed: 1730912
Obstet Gynecol. 2011 Jan;117(1):75-83
pubmed: 21173647
PLoS Med. 2011 Mar;8(3):e1001013
pubmed: 21445332
BJOG. 2010 Mar;117(4):456-62
pubmed: 20074261
Genesis. 2009 Dec;47(12):793-8
pubmed: 19830817
Hypertension. 2012 Sep;60(3):712-21
pubmed: 22868393
Science. 2000 Jan 21;287(5452):408
pubmed: 10671158
J Am Assoc Lab Anim Sci. 2016;55(4):467-74
pubmed: 27423155
Mol Immunol. 2010 Apr;47(7-8):1500-6
pubmed: 20181396
Clin Exp Immunol. 2014 Sep;177(3):743-9
pubmed: 24802103
Obstet Gynecol. 2000 Dec;96(6):950-5
pubmed: 11084184
Front Immunol. 2012 Mar 19;3:55
pubmed: 22566936