母体营养不足对后代颈动脉重塑的长期影响:miR-29c的作用
Long-term effects of maternal undernutrition on offspring carotid artery remodeling: role of miR-29c.
作者信息
Khorram O, Chuang T D, Pearce W J
机构信息
1Department of Obstetrics and Gynecology,Harbor-UCLA Medical Center,Torrance,CA,USA.
2Department of Physiology and Center for Perinatal Biology,Loma Linda University,CA,USA.
出版信息
J Dev Orig Health Dis. 2015 Aug;6(4):342-9. doi: 10.1017/S2040174415001208. Epub 2015 May 26.
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.
本研究的目的是检验以下假设
母体营养不良时母体糖皮质激素过量可能通过miR-29c调控细胞外基质(ECM)成分的表达。我们测量了三组母鼠后代颈动脉中胶原蛋白3A1、胶原蛋白4A5和基质金属蛋白酶2(MMP2)的mRNA(qRT-PCR)和蛋白质(蛋白质免疫印迹法)表达:在妊娠后半期食物摄入量限制为50%的母鼠[母体营养不良(MUN)组]、从妊娠第10天至足月在饮用水中摄入甲吡酮(MET)(500 mg/ml)的MUN母鼠,以及自由采食的对照母鼠。MUN组颈动脉在3周、3个月和9个月时miR-29c表达显著降低,而MET处理母鼠可部分阻断这些表达降低。作为miR-29c靶标的ECM基因的表达模式与miR-29c表达相关。在3周龄的MUN组颈动脉中,弹性蛋白(ELN)和MMP2 mRNA的表达增加;在9月龄的颈动脉中,Col3A1和Col4A5的表达也显著增加。MET处理可阻断3周和9个月时ECM基因mRNA表达的这些变化。同样,3周龄时MUN组颈动脉中ELN和MMP2蛋白的表达增加,到9个月时,Col3A1和Col4A5的表达也增加,而MET可阻断MUN组颈动脉中的这些增加。总体而言,结果表明miR-29c与其靶标ECM蛋白的表达密切相关,从而支持了我们的核心假设。
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