ArticleHypertension research : official journal of the Japanese Society of Hypertension2024
Roles of the mechanosensitive ion channel Piezo1 in the renal podocyte injury of experimental hypertensive nephropathy.
Article in Hypertension research : official journal of the Japanese Society of Hypertension, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27 citing papers in PubMed, 33 citations in OpenAlex.
- The Mechano-Immune-Vascular Activation Loop: An Integrative Conceptual Framework for Positive Feedback in Hypertension.International journal of molecular sciences · 2026Review
- The extracellular matrix Piezo1 feedback loop drives renal fibrosis through compartment-specific mechanotransduction.International urology and nephrology · 2026Review
- Elevated Piezo levels cause structural and functional alterations inLife science alliance · 2026Article
- Piezo1-Mediated Mechanotransduction: Orchestrating the Dynamic Response of Podocytes and Parietal Epithelial Cells to Mechanical Stress.Acta physiologica (Oxford, England) · 2026Review
- Piezo1 and podocyte mechano-sensing in hypertensive nephropathy.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Article
- Podocyte-specific deletion of mechanochannel Piezo1 exacerbates proteinuria and podocyte injury in mouse hypertensive nephropathy.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Article
- Molecular mechanisms in podocytopathies: finding suitable targets for a new era of glomerular gene therapy.Clinical kidney journal · 2026Review
- From plasma membrane to lysosomes: expanding roles of TMEM63/OSCA channels in mechanosensation and intracellular signaling.Frontiers in pharmacology · 2026Review
- PIEZO Force Sensing in Vascular Biology: An Explosion of New Knowledge, Concepts and Opportunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Mechanical Stress and Protective Mechanisms in Podocytes: Insights into Hypertensive Nephropathy.International journal of molecular sciences · 2025Review
- Mechanisms and Therapeutic Perspectives of Podocyte Aging in Podocytopathies.International journal of molecular sciences · 2025Review
- Beyond Blood Pressure: Emerging Pathways and Precision Approaches in Hypertension-Induced Kidney Damage.International journal of molecular sciences · 2025Review
- New Discoveries in Podocyte Mechanosensing and Mechanotransduction.Journal of the American Society of Nephrology : JASN · 2025Article
- The intelligent podocyte: sensing and responding to a complex microenvironment.Nature reviews. Nephrology · 2025Review
- Alternative Splicing in Mechanically Stretched Podocytes as a Model of Glomerular Hypertension.Journal of the American Society of Nephrology : JASN · 2025Article
- Endothelial Piezo1 stimulates angiogenesis to offer protection against intestinal ischemia-reperfusion injury in mice.Molecular medicine (Cambridge, Mass.) · 2025Article
- Piezo1, F-Actin Remodeling, and Podocyte Survival and Regeneration.Journal of the American Society of Nephrology : JASN · 2025Article
- A new mechanism of diabetic kidney disease progression by Piezo proteins: mediators between mechanical stimuli and fibrosis.Hypertension research : official journal of the Japanese Society of Hypertension · 2025Article
- Piezo, Nephrocyte Function, and Slit Diaphragm Maintenance in Drosophila.Journal of the American Society of Nephrology : JASN · 2025Article
- PIEZO1-Mediated Calcium Signaling and Podocyte Injury in Diabetic Kidney Disease.Journal of the American Society of Nephrology : JASN · 2025Article
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5 authors at 2 institutions in 1 country.
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Abstract
Glomerular podocyte injury plays an essential role in proteinuria pathogenesis, a hallmark of chronic kidney disease, including hypertensive nephropathy. Although podocytes are susceptible to mechanical stimuli, their mechanotransduction pathways remain elusive. Piezo proteins, including Piezo1 and 2, are mechanosensing ion channels that mediate various biological phenomena. Although renal Piezo2 expression and its alteration in rodent dehydration and hypertension models have been reported, the role of Piezo1 in hypertensive nephropathy and podocyte injury is unclear. In this study, we examined Piezo1 expression and localization in the kidneys of control mice and in those of mice with hypertensive nephrosclerosis. Uninephrectomized, aldosterone-infused, salt-loaded mice developed hypertension, albuminuria, podocyte injury, and glomerulosclerosis. RNAscope in situ hybridization revealed that Piezo1 expression was enhanced in the podocytes, mesangial cells, and distal tubular cells of these mice compared to those of the uninephrectomized, vehicle-infused control group. Piezo1 upregulation in the glomeruli was accompanied by the induction of podocyte injury-related markers, plasminogen activator inhibitor-1 and serum/glucocorticoid regulated kinase 1. These changes were reversed by antihypertensive drug. Exposure of Piezo1-expressing cultured podocytes to mechanical stretch activated Rac1 and upregulated the above-mentioned markers, which was antagonized by the Piezo1 blocker grammostola mechanotoxin #4 (GsMTx4). Administration of Piezo1-specific agonist Yoda1 mimicked the effects of mechanical stretch, which was minimized by the Yoda1-specific inhibitor Dooku1 and Rac inhibitor. Rac1 was also activated in the above-mentioned hypertensive mice, and Rac inhibitor downregulated gene expression of podocyte injury-related markers in vivo. Our results suggest that Piezo1 plays a role in mechanical stress-induced podocyte injury.
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