ArticleThe Journal of clinical investigation2024
Single-cell transcriptomics and chromatin accessibility profiling elucidate the kidney-protective mechanism of mineralocorticoid receptor antagonists.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- Targeting the aldosterone-mineralocorticoid receptor pathway in cardiovascular-kidney-metabolic syndrome.Nature reviews. Nephrology · 2026Review
- The interplay of bosentan and finerenone in amelioration of cardiac dysfunction within benign prostatic hyperplasia in rats.Molecular biology reports · 2026Article
- Tubular epithelial cells promote macrophage pyroptosis through PANX1-extracellular ATP-P2X7 signaling in aldosterone-dependent renal injury.Cell death & disease · 2026Article
- Zinc Signaling in Acute Kidney Injury.Cells · 2026Review
- Urokinase Promotes Redundantly Intratubular C3a-Formation But Not ENaC-Driven Hypertension in DOCA/Salt Kidney Injury.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Chromatin remodeling and epigenetic regulation in chronic kidney disease.Frontiers in genetics · 2026Review
- Loss of KLF15 expression characterizes proximal tubule injury in cisplatin-induced acute kidney injury: A multi-omics study.Current research in toxicology · 2026Article
- Melatonin Administration Attenuates High-Fat-Diet-Induced Renal Damage in Wistar Rats.Biomolecules · 2025Article
- Single-cell RNA sequencing revealed the association between proximal tubular epithelial cells and renal interstitial cells in chronic kidney disease progression.Scientific reports · 2025Article
- The nonsteroidal MR antagonist finerenone reverses Western diet-induced kidney disease by regulating mitochondrial and lipid metabolism and inflammation.American journal of physiology. Renal physiology · 2025Article
- Real-world use of finerenone in diabetic kidney disease: eGFR slope analysis with exploratory data on prior MRA use.Diabetology international · 2025Article
- Analysis of individual patient pathway coordination in a cross-species single-cell kidney atlas.Nature genetics · 2025Article
- Pathogenesis and Therapeutic Perspectives of Tubular Injury in Diabetic Kidney Disease: An Update.Biomedicines · 2025Review
- The Omics-Driven Machine Learning Path to Cost-Effective Precision Medicine in Chronic Kidney Disease.Proteomics · 2025Review
- The actin and microtubule network regulator WHAMM is identified as a key kidney disease risk gene.Cell reports · 2025Article
- Mineralocorticoid receptor antagonism for non-diabetic kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- Nonsteroidal MR antagonism in PA: clinical outcomes and unanswered questions.Hypertension research : official journal of the Japanese Society of Hypertension · 2025Article
- The immune duality of osteopontin and its therapeutic implications for kidney transplantation.Frontiers in immunology · 2025Review
- Hydronephrosis-Associated Renal Fibrosis: Clinical Validation of Spp1 as a Biomarker and Therapeutic Target.Kidney & blood pressure research · 2025Article
- The Kidney Precision Medicine Project and Single-Cell Biology of the Injured Proximal Tubule.The American journal of pathology · 2025Review
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 3 countries.
Funding
Abstract
Mineralocorticoid excess commonly leads to hypertension (HTN) and kidney disease. In our study, we used single-cell expression and chromatin accessibility tools to characterize the mineralocorticoid target genes and cell types. We demonstrated that mineralocorticoid effects were established through open chromatin and target gene expression, primarily in principal and connecting tubule cells and, to a lesser extent, in segments of the distal convoluted tubule cells. We examined the kidney-protective effects of steroidal and nonsteroidal mineralocorticoid antagonists (MRAs), as well as of amiloride, an epithelial sodium channel inhibitor, in a rat model of deoxycorticosterone acetate, unilateral nephrectomy, and high-salt consumption-induced HTN and cardiorenal damage. All antihypertensive therapies protected against cardiorenal damage. However, finerenone was particularly effective in reducing albuminuria and improving gene expression changes in podocytes and proximal tubule cells, even with an equivalent reduction in blood pressure. We noted a strong correlation between the accumulation of injured/profibrotic tubule cells expressing secreted posphoprotein 1 (Spp1), Il34, and platelet-derived growth factor subunit b (Pdgfb) and the degree of fibrosis in rat kidneys. This gene signature also showed a potential for classifying human kidney samples. Our multiomics approach provides fresh insights into the possible mechanisms underlying HTN-associated kidney disease, the target cell types, the protective effects of steroidal and nonsteroidal MRAs, and amiloride.
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