Mechanisms of impaired nephrogenesis with fetal growth restriction: altered renal transcription and growth factor expression.

Mechanisms of impaired nephrogenesis with fetal growth restriction: altered renal transcription and growth factor expression.
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DOI:
10.1016/j.ajog.2008.05.018
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发表时间:
2008-09
影响因子:
9.8
通讯作者:
Nast, Cynthia C.
Nast, Cynthia C.
中科院分区:
医学1区
文献类型:
--
作者:
Abdel-Hakeem, Ahmed K.;Henry, Tasmia Q.;Magee, Thomas R.;Desai, Mina;Ross, Michael G.;Mansano, Roy Z.;Torday, John S.;Nast, Cynthia C.

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母亲在怀孕期间的食物限制导致生长受限的新生儿和肾小球数量减少,有助于程序性后代高血压。我们研究了是否减少肾发生可能是由控制输尿管芽分支和间充质上皮转化的因素失调编程。妊娠10 - 20天,Sprague道利妊娠大鼠(n=6/组)自由进食; FR大鼠50%限食。在胚胎第20天,WT 1,Pax 2,FGF 2,GDNF,cRET,WNT 4,WNT 11,BMP 4,BMP 7和FGF 7的mRNA和蛋白质表达通过实时PCR和Western印迹法测定。母体FR导致WT 1、FGF 2和BMP 7的mRNA表达上调,而Pax 2、GDNF、FGF 7、BMP 4、WNT 4和WNT 11的mRNA表达下调。WT 1、GDNF、Pax 2、FGF 7、BMP 4和WNT 4的蛋白表达一致。母体FR改变了胎儿肾脏转录和生长因子的基因表达,并可能有助于后代高血压的发展。
Maternal food restriction during pregnancy results in growth restricted newborns and reduced glomerular number, contributing to programmed offspring hypertension. We investigated whether reduced nephrogenesis may be programmed by dysregulation of factors controlling ureteric bud branching and mesenchyme to epithelial transformation. 10 to 20 days gestation, Sprague Dawley pregnant rats (n=6/group) received ad libitum food; FR rats were 50% food restricted. At embryonic day 20, mRNA and protein expression of WT1, Pax2, FGF2, GDNF, cRET, WNT4, WNT11, BMP4, BMP7, and FGF7 were determined by real-time PCR and Western blotting. Maternal FR resulted in up-regulated mRNA expression for WT1, FGF2, and BMP7 whereas Pax2, GDNF, FGF7, BMP4, WNT4, and WNT11 mRNAs were down-regulated. Protein expression was concordant for WT1, GDNF, Pax2, FGF7, BMP4 and WNT4. Maternal FR altered gene expression of fetal renal transcription and growth factors, and likely contributes to development of offspring hypertension.
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