独特的miRNome和转录组图谱是小鼠肾脏微血管异质性的基础。

IF 3.7 2区 医学 Q1 PHYSIOLOGY American Journal of Physiology-renal Physiology Pub Date : 2023-09-01 Epub Date: 2023-07-06 DOI:10.1152/ajprenal.00005.2023
Matthijs Luxen, Peter J Zwiers, Femke Meester, Rianne M Jongman, Timara Kuiper, Jill Moser, Marianne Pultar, Susanna Skalicky, Andreas B Diendorfer, Matthias Hackl, Matijs van Meurs, Grietje Molema
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引用次数: 1

摘要

肾脏血管中的内皮细胞根据其所处的(微)血管床发挥不同的功能。本研究旨在研究这些差异背后的微小RNA和mRNA转录模式。在小RNA和RNA测序分析之前,我们通过激光显微切割微血管来放大小鼠肾皮质中的微血管区室。通过这些方法,我们表征了小动脉、肾小球、管周毛细血管和毛细血管后小静脉的微小RNA和mRNA转录谱。定量RT-PCR、原位杂交和免疫组织化学用于验证测序结果。在所有微血管隔室中都发现了独特的微小RNA和mRNA转录谱,专用标记物微小RNA和信使核糖核酸在单个微血管隔室内显示出富集的转录。原位杂交验证了微小RNA mmu-miR-140-3p在小动脉中、mmu-miR-322-3p在肾小球中和mmu-miR-451a在毛细血管后小静脉中的定位。免疫组织化学染色显示von Willebrand因子蛋白主要在小动脉和毛细血管后小静脉中表达,而GABRB1在肾小球中富集,IGF1在毛细血管后小血管中富集。已鉴定出550多个具有微血管行为功能意义的隔室特异性microRNA-mRNA相互作用对。总之,我们的研究确定了小鼠肾皮质微血管区室中独特的微小RNA和mRNA转录模式,这是微血管异质性的基础。这些模式为未来研究健康和疾病中微血管参与的差异提供了重要的分子信息。新的和值得注意的是,肾内皮细胞表现出高度的异质性,这取决于它们所处的(微)血管床。导致这些差异的分子基础尚不清楚,但对于提高对健康和疾病中肾脏微血管参与的理解具有重要意义。本报告描述了小鼠肾皮质微血管床的m(micro)RNA表达谱,揭示了微血管隔室特异性m(Micro)RNA和miRNA-mRNA对,从而揭示了肾微血管异质性的重要分子机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Unique miRNome and transcriptome profiles underlie microvascular heterogeneity in mouse kidney.

Endothelial cells in blood vessels in the kidney exert different functions depending on the (micro)vascular bed they are located in. The present study aimed to investigate microRNA and mRNA transcription patterns that underlie these differences. We zoomed in on microvascular compartments in the mouse renal cortex by laser microdissecting the microvessels prior to small RNA- and RNA-sequencing analyses. By these means, we characterized microRNA and mRNA transcription profiles of arterioles, glomeruli, peritubular capillaries, and postcapillary venules. Quantitative RT-PCR, in situ hybridization, and immunohistochemistry were used to validate sequencing results. Unique microRNA and mRNA transcription profiles were found in all microvascular compartments, with dedicated marker microRNAs and mRNAs showing enriched transcription in a single microvascular compartment. In situ hybridization validated the localization of microRNAs mmu-miR-140-3p in arterioles, mmu-miR-322-3p in glomeruli, and mmu-miR-451a in postcapillary venules. Immunohistochemical staining showed that von Willebrand factor protein was mainly expressed in arterioles and postcapillary venules, whereas GABRB1 expression was enriched in glomeruli, and IGF1 was enriched in postcapillary venules. More than 550 compartment-specific microRNA-mRNA interaction pairs were identified that carry functional implications for microvascular behavior. In conclusion, our study identified unique microRNA and mRNA transcription patterns in microvascular compartments of the mouse kidney cortex that underlie microvascular heterogeneity. These patterns provide important molecular information for future studies into differential microvascular engagement in health and disease.NEW & NOTEWORTHY Renal endothelial cells display a high level of heterogeneity depending on the (micro)vascular bed they reside in. The molecular basis contributing to these differences is poorly understood yet of high importance to increase understanding of microvascular engagement in the kidney in health and disease. This report describes m(icro)RNA expression profiles of microvascular beds in the mouse renal cortex and uncovers microvascular compartment-specific m(icro)RNAs and miRNA-mRNA pairs, thereby revealing important molecular mechanisms underlying renal microvascular heterogeneity.

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来源期刊
CiteScore
8.40
自引率
7.10%
发文量
154
审稿时长
2-4 weeks
期刊介绍: The American Journal of Physiology - Renal Physiology publishes original manuscripts on timely topics in both basic science and clinical research. Published articles address a broad range of subjects relating to the kidney and urinary tract, and may involve human or animal models, individual cell types, and isolated membrane systems. Also covered are the pathophysiological basis of renal disease processes, regulation of body fluids, and clinical research that provides mechanistic insights. Studies of renal function may be conducted using a wide range of approaches, such as biochemistry, immunology, genetics, mathematical modeling, molecular biology, as well as physiological and clinical methodologies.
期刊最新文献
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