Inflammatory Alterations to Renal Lymphatic Endothelial Cell Gene Expression in Mouse Models of Hypertension.

IF 2.3 4区医学 Q2 PERIPHERAL VASCULAR DISEASE

Kidney & blood pressure research Pub Date : 2024-01-01 Epub Date: 2024-07-22 DOI:10.1159/000539721

Justin G McDermott, Bethany L Goodlett, Heidi A Creed, Shobana Navaneethabalakrishnan, Joseph M Rutkowski, Brett M Mitchell

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引用次数: 0

Abstract

Introduction: Hypertension (HTN) is a major cardiovascular disease that can cause and be worsened by renal damage and inflammation. We previously reported that renal lymphatic endothelial cells (LECs) increase in response to HTN and that augmenting lymphangiogenesis in the kidneys reduces blood pressure and renal pro-inflammatory immune cells in mice with various forms of HTN. Our aim was to evaluate the specific changes that renal LECs undergo in HTN.

Methods: We performed single-cell RNA sequencing. Using the angiotensin II-induced and salt-sensitive mouse models of HTN, we isolated renal CD31+ and podoplanin+ cells.

Results: Sequencing of these cells revealed three distinct cell types with unique expression profiles, including LECs. The number and transcriptional diversity of LECs increased in samples from mice with HTN, as demonstrated by 597 differentially expressed genes (p < 0.01), 274 significantly enriched pathways (p < 0.01), and 331 regulons with specific enrichment in HTN LECs. These changes demonstrate a profound inflammatory response in renal LECs in HTN, leading to an increase in genes and pathways associated with inflammation-driven growth and immune checkpoint activity in LECs.

Conclusion: These results reinforce and help to further explain the benefits of renal LECs and lymphangiogenesis in HTN.

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高血压小鼠模型中肾淋巴内皮细胞基因表达的炎性改变

导言：高血压（HTN）是一种主要的心血管疾病，可导致肾脏损伤和炎症，并使其恶化。我们以前曾报道过，肾脏淋巴内皮细胞（LECs）会随着高血压的发生而增加，而增强肾脏淋巴管的生成可降低血压，并减少各种形式高血压小鼠的肾脏促炎症免疫细胞。我们的目的是评估肾脏淋巴管在高血压肾病中发生的具体变化：我们进行了单细胞 RNA 测序。方法：我们进行了单细胞 RNA 测序，利用血管紧张素 II 诱导的高血压小鼠模型和盐敏感型高血压小鼠模型，我们分离了肾脏 CD31+ 和 podoplanin+ 细胞：结果：这些细胞的测序结果显示，包括 LECs 在内的三种细胞类型具有独特的表达谱。在患有高血压肾病的小鼠样本中，LECs 的数量和转录多样性增加了，这表现在 597 个差异表达基因（p<0.01）、274 个显著富集的通路（p<0.01）和 331 个在高血压肾病 LECs 中特异性富集的调控子。这些变化表明，在高血压肾病患者的肾脏LECs中存在深刻的炎症反应，导致LECs中与炎症驱动的生长和免疫检查点活性相关的基因和通路增加：这些结果加强并有助于进一步解释高血压肾脏淋巴管细胞和淋巴管生成的益处。

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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来源期刊

Kidney & blood pressure research 医学-泌尿学与肾脏学

CiteScore

4.80

自引率

3.60%

发文量

审稿时长

6-12 weeks

期刊介绍： This journal comprises both clinical and basic studies at the interface of nephrology, hypertension and cardiovascular research. The topics to be covered include the structural organization and biochemistry of the normal and diseased kidney, the molecular biology of transporters, the physiology and pathophysiology of glomerular filtration and tubular transport, endothelial and vascular smooth muscle cell function and blood pressure control, as well as water, electrolyte and mineral metabolism. Also discussed are the (patho)physiology and (patho) biochemistry of renal hormones, the molecular biology, genetics and clinical course of renal disease and hypertension, the renal elimination, action and clinical use of drugs, as well as dialysis and transplantation. Featuring peer-reviewed original papers, editorials translating basic science into patient-oriented research and disease, in depth reviews, and regular special topic sections, ''Kidney & Blood Pressure Research'' is an important source of information for researchers in nephrology and cardiovascular medicine.