Document Detail


EMMPRIN-mediated induction of uterine and vascular matrix metalloproteinases during pregnancy and in response to estrogen and progesterone.
MedLine Citation:
PMID:  23856290     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Pregnancy is associated with uteroplacental and vascular remodeling in order to adapt for the growing fetus and the hemodynamic changes in the maternal circulation. We have previously shown upregulation of uterine matrix metalloproteinases (MMPs) during pregnancy. Whether pregnancy-associated changes in MMPs are localized to the uterus or are generalized in feto-placental and maternal circulation is unclear. Also, the mechanisms causing the changes in uteroplacental and vascular MMPs during pregnancy are unclear. MMPs expression, activity and tissue distribution were measured in uterus, placenta and aorta of virgin, mid-pregnant (mid-Preg) and late pregnant (late-Preg) rats. Western blots and gelatin zymography revealed increases in MMP-2 and -9 in uterus and aorta of late-Preg compared with virgin and mid-Preg rats. In contrast, MMP-2 and -9 were decreased in placenta of late-Preg versus mid-Preg rats. Extracellular MMP inducer (EMMPRIN) was increased in uterus and aorta of pregnant rats, but was less in placenta of late-Preg than mid-Preg rats. Prolonged treatment of uterus or aorta of virgin rats with 17β-estradiol and progesterone increased the amount of EMMPRIN, MMP-2 and -9, and the sex hormone-induced increases in MMPs were prevented by EMMPRIN neutralizing antibody. Immunohistochemistry revealed that MMP-2 and -9 and EMMPRIN increased in uterus and aorta of pregnant rats, but decreased in placenta of late-Preg versus mid-Preg rats. Thus pregnancy-associated upregulation of uterine MMPs is paralleled by increased vascular MMPs, and both are mediated by EMMPRIN and induced by estrogen and progesterone, suggesting similar role of MMPs in uterine and vascular tissue remodeling and function during pregnancy. The decreased MMPs and EMMPRIN in placenta of late-Preg rats suggests reduced role of MMPs in feto-placental circulation during late pregnancy.
Authors:
Yiping Dang; Wei Li; Victoria Tran; Raouf A Khalil
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-07-13
Journal Detail:
Title:  Biochemical pharmacology     Volume:  86     ISSN:  1873-2968     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  2013 Sep 
Date Detail:
Created Date:  2013-09-03     Completed Date:  2013-10-29     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  734-47     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD147 / genetics*,  metabolism
Aorta / drug effects,  enzymology
Enzyme Induction / drug effects*
Estradiol / pharmacology*
Female
Gestational Age
Matrix Metalloproteinase 2 / genetics*,  metabolism
Matrix Metalloproteinase 9 / genetics*,  metabolism
Placenta / drug effects,  enzymology
Pregnancy
Pregnancy, Animal*
Progesterone / pharmacology*
Rats
Rats, Sprague-Dawley
Uterus / drug effects,  enzymology
Grant Support
ID/Acronym/Agency:
HD-60702/HD/NICHD NIH HHS; HL-111775/HL/NHLBI NIH HHS; HL-65998/HL/NHLBI NIH HHS; HL-98724/HL/NHLBI NIH HHS; R01 HL065998/HL/NHLBI NIH HHS; R03 HD060702/HD/NICHD NIH HHS; R21 HL098724/HL/NHLBI NIH HHS; R21 HL111775/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
136894-56-9/Antigens, CD147; 4G7DS2Q64Y/Progesterone; 4TI98Z838E/Estradiol; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.35/Matrix Metalloproteinase 9
Comments/Corrections

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