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鉴定介导小鼠肾脏在妊娠过程中适应性改变的结构和分子特征。

Identification of Structural and Molecular Signatures Mediating Adaptive Changes in the Mouse Kidney in Response to Pregnancy.

机构信息

Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.

Department of Animal Medicine and Surgery, Veterinary Faculty, Complutense University of Madrid, 28040 Madrid, Spain.

出版信息

Int J Mol Sci. 2022 Jun 3;23(11):6287. doi: 10.3390/ijms23116287.

Abstract

Pregnancy is characterized by adaptations in the function of several maternal body systems that ensure the development of the fetus whilst maintaining health of the mother. The renal system is responsible for water and electrolyte balance, as well as waste removal. Thus, it is imperative that structural and functional changes occur in the kidney during pregnancy. However, our knowledge of the precise morphological and molecular mechanisms occurring in the kidney during pregnancy is still very limited. Here, we investigated the changes occurring in the mouse kidney during pregnancy by performing an integrated analysis involving histology, gene and protein expression assays, mass spectrometry profiling and bioinformatics. Data from non-pregnant and pregnant mice were used to identify critical signalling pathways mediating changes in the maternal kidneys. We observed an expansion of renal medulla due to proliferation and infiltration of interstitial cellular constituents, as well as alterations in the activity of key cellular signalling pathways (e.g., AKT, AMPK and MAPKs) and genes involved in cell growth/metabolism (e.g., and ) in the kidneys during pregnancy. We also generated plasma and urine proteomic profiles, identifying unique proteins in pregnancy. These proteins could be used to monitor and study potential mechanisms of renal adaptations during pregnancy and disease.

摘要

妊娠的特征是母体多个身体系统的功能发生适应性改变,以确保胎儿的发育,同时维持母体的健康。肾脏系统负责水和电解质平衡以及废物清除。因此,在妊娠期间,肾脏的结构和功能必须发生变化。然而,我们对妊娠期间肾脏中发生的确切形态和分子机制的了解仍然非常有限。在这里,我们通过进行涉及组织学、基因和蛋白质表达分析、质谱分析和生物信息学的综合分析,研究了小鼠肾脏在妊娠期间发生的变化。我们使用未怀孕和怀孕小鼠的数据来鉴定介导母体肾脏变化的关键信号通路。我们观察到由于间质细胞成分的增殖和浸润,肾脏髓质扩张,以及参与细胞生长/代谢的关键细胞信号通路(如 AKT、AMPK 和 MAPKs)和基因(如 和 )的活性发生改变。我们还生成了血浆和尿液蛋白质组学图谱,鉴定了妊娠期间特有的蛋白质。这些蛋白质可用于监测和研究妊娠和疾病期间肾脏适应的潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd27/9181623/d5b87773521b/ijms-23-06287-g001.jpg

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