Single-Cell Transcriptome Sequencing Reveals Molecular Mechanisms of Renal Injury in Essential Hypertension

Abstract

Introduction: Hypertensive nephropathy is characterized by glomerular and tubulointerstitial damage, but we know little about changes in cell-specific gene expression in the early stages of hypertensive kidney injury, which usually has no obvious pathological changes. Methods: We performed unbiased single-cell RNA sequencing of rat kidney samples from hypertensive kidney injury to generate 10602 single-cell transcriptomes from 2 control and 2 early stage of hypertensive kidney injury samples. Results: All major cell types of the kidney were represented in the final dataset. Side-by-side comparisons showed that cell type-specific changes in gene expression are critical for functional impairment of glomeruli and tubules and activation of immune cells. In particular, we found a significantly reduced gene expression profile of maintaining vascular integrity in glomerular cells of hypertensive kidney injury. Meanwhile, the expression of genes associated with oxidative stress injury and fibrosis in the renal tubules and collecting ducts was elevated, but the degree of tubular cells response to injury differed between parts. We also found a signature of immune cell infiltration in hypertensive kidney injury. Discussion/Conclusion: Exploring the changes of gene expression in hypertension-injured kidneys may be helpful to identify the early biomarkers and signal pathways of this disease. Our data provide rich resources for understanding the pathogenesis of hypertensive renal injury and formulating effective treatment strategies.

The relationship between dietary inflammatory index (DII) and early renal injury in population with/without hypertension: analysis of the National health and nutrition examination survey 2001–2002

“…Inflammation is believed to play a pivotal role in the intricate relationship between hypertension, diet, and renal health. Animal studies have demonstrated that hypertension can induce glomerular injury by compromising the integrity of the glomerular capillaries and exacerbating local renal inflammation [ 55 ]. The tissue damage triggered by hypertension can stimulate the generation or presentation of antigens, leading to an immune response and stimulates the release of inflammatory mediators [ 53 ].…”