Tissue-specific changes in pregnancy associated plasma protein-A expression with age in mice.

Tissue-specific changes in pregnancy associated plasma protein-A expression with age in mice.
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DOI:
10.1016/j.exger.2014.04.011
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发表时间:
2014-09
影响因子:
3.9
通讯作者:
Conover, Cheryl A.
Conover, Cheryl A.
中科院分区:
医学2区
文献类型:
--
作者:
Harstad, Sara L.;Conover, Cheryl A.

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妊娠相关血浆蛋白A(PAPP-A)是一种新型的锌金属蛋白酶,在妊娠外的许多系统中发挥作用。人类和小鼠的数据表明PAPP-A在衰老和年龄相关疾病中的作用。然而,我们对组织特异性PAPP-A表达和这种表达随年龄的可能变化的了解是有限的。因此,本研究的目的是使用实时PCR确定雄性和雌性小鼠多个组织中PAPP-A mRNA表达随年龄的变化。这些包括心脏、肝脏、肾脏、骨骼、脂肪、骨骼肌、性腺、大脑、胸腺和脾脏。在年轻小鼠中,PAPP-A mRNA在除肝脏外的所有组织中均以相对较高的水平表达。雄性和雌性之间表达的唯一差异见于肾脏、皮下脂肪和性腺。内脏脂肪中PAPP-A mRNA表达水平最高,是皮下脂肪的10倍。PAPP-A在肾脏、脑和性腺中的表达随年龄的增长而显著增加。PAPP-A在骨和骨骼肌中的表达随年龄增长而显著下降。在胸腺中,PAPP-A mRNA随年龄增长呈双相反应。在检查的任何其他组织中均未观察到PAPP-A表达的年龄相关变化。胰岛素样生长因子I(IGF-I)生物活性的标志物IGFBP-5 mRNA的表达已知受PAPP-A调节,其在肾脏、骨骼、骨骼肌和胸腺中表达随年龄的变化。因此,组织特异性PAPP-A在小鼠中的表达在衰老过程中受到不同的影响,并可能调节某些组织中局部IGF-I的生物活性。
Pregnancy-associated plasma protein-A (PAPP-A) is a novel zinc metalloproteinase that functions in many systems outside of pregnancy. Data in both humans and mice suggest a role for PAPP-A in aging and age-related diseases. However, our knowledge of tissue-specific PAPP-A expression and possible changes in this expression with age is limited. Thus, the aim of this study was to determine PAPP-A mRNA expression in multiple tissues with age in both male and female mice using real-time PCR. These included heart, liver, kidney, bone, fat, skeletal muscle, gonads, brain, thymus and spleen. In young mice, PAPP-A mRNA was expressed at relatively high levels in all tissues examined except for liver. The only difference in expression between males and females was seen in kidney, subcutaneous fat and gonads. The highest PAPP-A mRNA expression levels were found in visceral fat and these were 10-fold higher than in subcutaneous fat. PAPP-A expression significantly increased with age in kidney, brain and gonads. PAPP-A expression significantly deceased with age in bone and skeletal muscle. In the thymus, PAPP-A mRNA showed a biphasic response with age. There were no age-related changes in PAPP-A expression seen in any of the other tissues examined. Expression of IGFBP-5 mRNA, a marker of insulin-like growth factorI (IGF-I) bioactivity known to be regulated by PAPP-A, paralleled the changes in PAPP-A expression with age in kidney, bone, skeletal muscle and thymus. Thus, tissue-specific PAPP-A expression in mice is differentially affected during aging, and may regulate local IGF-I bioactivity in certain tissues.
DOI: 10.1530/joe-13-0167
发表时间: 2013-10
期刊: The Journal of endocrinology
影响因子: --
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Mader JR;Resch ZT;McLean GR;Mikkelsen JH;Oxvig C;Marler RJ;Conover CA
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