Department of Medicine, University of Verona, Verona, Italy.
Front Endocrinol (Lausanne). 2023 Mar 29;14:1155011. doi: 10.3389/fendo.2023.1155011. eCollection 2023.
Urinary extracellular vesicles (uEVs), released from cells of the urogenital tract organs, carry precious information about originating tissues. The study of molecules transported through uEVs such as proteins, lipids and nucleic acids provides a deeper understanding of the function of the kidney, an organ involved in the pathogenesis of hypertension and a target of hypertension-mediated organ damage. Molecules derived from uEVs are often proposed for the study of disease pathophysiology or as possible disease diagnostic and prognostic biomarkers. Analysis of mRNA loading within uEVs may be a unique and readily obtainable way to assess gene expression patterns of renal cells, otherwise achievable only by an invasive biopsy procedure. Interestingly, the only few studies investigating transcriptomics of hypertension-related genes through the analysis of mRNA from uEVs are inherent to mineralocorticoid hypertension. More specifically, it has been observed that perturbation in human endocrine signalling through mineralcorticoid receptors (MR) activation parallels changes of mRNA transcripts in urine supernatant. Furthermore, an increased copy number of uEVs-extracted mRNA transcripts of the 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) gene were detected among subjects affected by apparent mineralocorticoid excess (AME), a hypertension-inducing autosomal recessive disorder due to a defective enzyme function. Moreover, by studying uEVs mRNA, it was observed that the renal sodium chloride cotransporter (NCC) gene expression is modulated under different conditions related to hypertension. Following this perspective, we illustrate here the state of the art and the possible future of uEVs transcriptomics towards a deeper knowledge of hypertension pathophysiology and ultimately more tailored investigational, diagnostic-prognostic approaches.
尿细胞外囊泡（uEVs）由泌尿生殖道器官的细胞释放，携带有关起源组织的宝贵信息。研究通过 uEVs 转运的分子，如蛋白质、脂质和核酸，可以更深入地了解肾脏的功能，肾脏是高血压发病机制的一个器官，也是高血压介导的器官损伤的靶器官。源自 uEVs 的分子通常被提议用于研究疾病的病理生理学，或作为可能的疾病诊断和预后生物标志物。分析 uEVs 内的 mRNA 负载可能是一种独特且易于获得的方法，可评估肾脏细胞的基因表达模式，否则只能通过侵入性活检程序来实现。有趣的是，仅通过分析 uEVs 中的 mRNA 来研究与高血压相关的基因转录组学的少数几项研究是固有的醛固酮高血压。更具体地说，已经观察到通过激活盐皮质激素受体（MR）干扰人类内分泌信号与尿液上清液中 mRNA 转录本的变化平行。此外，在患有明显醛固酮过多症（AME）的受试者中检测到尿液外泌体提取的 mRNA 转录本的 11β-羟类固醇脱氢酶 2（HSD11B2）基因的拷贝数增加，AME 是一种由于酶功能缺陷引起的导致高血压的常染色体隐性遗传疾病。此外，通过研究 uEVs mRNA，观察到在与高血压相关的不同条件下，肾脏钠氯共转运蛋白（NCC）基因表达受到调节。基于这一观点，我们在这里说明了 uEVs 转录组学的最新技术和可能的未来，以更深入地了解高血压病理生理学，并最终更有针对性地进行研究、诊断和预后方法。
