title: Long-term effects of maternal undernutrition on offspring carotid artery remodeling: role of miR-29c.
abstract: The purpose of this study was to examine the hypothesis that excess maternal glucocorticoids in response to maternal undernutrition programs the expression of extracellular matrix (ECM) components potentially by miR-29c. We measured the expression of mRNA (qRT-PCR) and protein (Western blot) for collagen 3A1, collagen 4A5 and matrix metalloproteinase 2 (MMP2) in offspring carotid arteries from three groups of dams: 50% food-restricted in latter half of gestation [maternal undernutrition (MUN)], MUN dams who received metyrapone (MET) (500 mg/ml ) in drinking water from day 10 of gestation to term, and control dams fed an ad libitum diet. The expression of miR-29c was significantly decreased at 3 weeks, 3 months and 9 months in MUN carotid arteries, and these decreases in expression were partially blocked by treatment of dams with MET. The expression pattern of ECM genes that are targets of miR-29c correlated with miR-29c expression. Expression of mRNA was increased for elastin (ELN) and MMP2 mRNA in 3-week MUN carotids; in 9-month carotids there were also significant increases in expression of Col3A1 and Col4A5. These changes in mRNA expression of ECM genes at 3 weeks and 9 months were blocked by MET treatment. Similarly, the expression of ELN and MMP2 proteins at 3 weeks were increased in MUN carotids, and by 9 months there were also increases in expression of Col3A1 and Col4A5, which were blocked by MET in MUN carotids. Overall, the results demonstrate a close correlation between expression of miR-29c and the ECM proteins that are its targets thus supporting our central hypothesis.
authors.affiliation: 1Department of Obstetrics and Gynecology,Harbor-UCLA Medical Center,Torrance,CA,USA.
authors.forename: O
authors.initials: O
authors.lastname: Khorram
authors.affiliation: 1Department of Obstetrics and Gynecology,Harbor-UCLA Medical Center,Torrance,CA,USA.
authors.forename: T D
authors.initials: TD
authors.lastname: Chuang
authors.affiliation: 2Department of Physiology and Center for Perinatal Biology,Loma Linda University,CA,USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Pearce
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000378:metabolism*; D024061:Collagen Type III / Q000378:metabolism; D004549:Elastin / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D048070:Fetal Nutrition Disorders / Q000378:metabolism*; D005938:Glucocorticoids / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D011247:Pregnancy; D039401:Prenatal Nutritional Physiological Phenomena; D017207:Rats, Sprague-Dawley
chemical_list: D024061:Collagen Type III; D016326:Extracellular Matrix Proteins; D005938:Glucocorticoids; C526366:MIRN29 microRNA, rat; D035683:MicroRNAs; D004549:Elastin; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat
keywords: carotid remodeling; extracellular matrix; fetal programming; miR-29c