ArticleScientific reports2019
Cerebral ischemia induces TRPC6 via HIF1α/ZEB2 axis in the glomerular podocytes and contributes to proteinuria.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- Transient Middle Cerebral Artery Occlusion in Rats as a Nonclinical Model of Ischemic Stroke: A Systematic Review.Current issues in molecular biology · 2026Review
- Identification of Hypoxia-ALCAMAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Stroke and Distal Organ Damage: Exploring Brain-Kidney Crosstalk.Neurochemical research · 2024Review
- Article
- Thrombotic Alterations under Perinatal Hypoxic Conditions: HIF and Other Hypoxic Markers.International journal of molecular sciences · 2023Review
- The Role of Hypoxia on the Trimethylation of H3K27 in Podocytes.Biomedicines · 2023Article
- Insight into the Molecular Mechanism of Diabetic Kidney Disease and the Role of Metformin in Its Pathogenesis.International journal of molecular sciences · 2023Review
- Hypoxia-Inducible Factors and Diabetic Kidney Disease-How Deep Can We Go?International journal of molecular sciences · 2022Review
- Detrimental effects of hypoxia on glomerular podocytes.Journal of physiology and biochemistry · 2021Review
- Evolutionary conservation of intrinsically unstructured regions in slit-diaphragm proteins.PloS one · 2021Article
- Review
- TRP Channels Regulation of Rho GTPases in Brain Context and Diseases.Frontiers in cell and developmental biology · 2020Review
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Podocytes are specialized cells of the glomerulus and key component of the glomerular filtration apparatus (GFA). GFA regulates the permselectivity and ultrafiltration of blood. The mechanism by which the integrity of the GFA is compromised and manifest in proteinuria during ischemic stroke remains enigmatic. We investigated the mechanism of ischemic hypoxia-induced proteinuria in a middle cerebral artery occlusion (MCAO) model. Ischemic hypoxia resulted in the accumulation of HIF1α in the podocytes that resulted in the increased expression of ZEB2 (Zinc finger E-box-binding homeobox 2). ZEB2, in turn, induced TRPC6 (transient receptor potential cation channel, subfamily C, member 6), which has increased selectivity for calcium. Elevated expression of TRPC6 elicited increased calcium influx and aberrant activation of focal adhesion kinase (FAK) in podocytes. FAK activation resulted in the stress fibers reorganization and podocyte foot process effacement. Our study suggests overactive HIF1α/ZEB2 axis during ischemic-hypoxia raises intracellular calcium levels via TRPC6 and consequently altered podocyte structure and function thus contributes to proteinuria.
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