ArticleJournal of the American Society of Nephrology : JASN2011
Glutamatergic signaling maintains the epithelial phenotype of proximal tubular cells.
Article in Journal of the American Society of Nephrology : JASN, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 47 citations in OpenAlex.
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- Comprehensive mapping of sensory and sympathetic innervation of the developing kidney.Cell reports · 2024Article
- Human pluripotent stem cell-derived kidney organoids reveal tubular epithelial pathobiology of heterozygous HNF1B-associated dysplastic kidney malformations.Stem cell reports · 2024Article
- Comprehensive mapping of sensory and sympathetic innervation of the developing kidney.bioRxiv : the preprint server for biology · 2024Article
- microRNA Expression Profile in Obesity-Induced Kidney Disease Driven by High-Fat Diet in Mice.Nutrients · 2024Article
- HK-2 cell response to TGF-β highly depends on cell culture medium formulations.Histochemistry and cell biology · 2024Article
- Ion channels and channelopathies in glomeruli.Physiological reviews · 2023Review
- Elimination of Vitamin D Signaling Causes Increased Mortality in a Model of Overactivation of the Insulin Receptor: Role of Lipid Metabolism.Nutrients · 2022Article
- PTEN Deletion in Adult Mice Induces Hypoinsulinemia With Concomitant Low Glucose Levels.Frontiers in endocrinology · 2022Article
- Role of microRNAs in Obesity-Related Kidney Disease.International journal of molecular sciences · 2021Review
- Extracellular Vesicles and Renal Fibrosis: An Odyssey toward a New Therapeutic Approach.International journal of molecular sciences · 2021Review
- NMDA receptor-mediated CaMKII/ERK activation contributes to renal fibrosis.BMC nephrology · 2020Article
- Glutamate-Gated NMDA Receptors: Insights into the Function and Signaling in the Kidney.Biomolecules · 2020Review
- Protective role of renal proximal tubular alpha-synuclein in the pathogenesis of kidney fibrosis.Nature communications · 2020Article
- Article
- Ketamine suppresses hypoxia-induced inflammatory responses in the late-gestation ovine fetal kidney cortex.The Journal of physiology · 2016Article
- Intragraft transcriptional profiling of renal transplant patients with tubular dysfunction reveals mechanisms underlying graft injury and recovery.Human genomics · 2016Article
- Article
- Unilateral ureteral obstruction: beyond obstruction.International urology and nephrology · 2014Review
- A combinatorial approach of Proteomics and Systems Biology in unravelling the mechanisms of acute kidney injury (AKI): involvement of NMDA receptor GRIN1 in murine AKI.BMC systems biology · 2013Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epithelial-mesenchymal transition (EMT) contributes to the progression of renal tubulointerstitial fibrosis. The N-methyl-d-aspartate receptor (NMDAR), which is present in proximal tubular epithelium, is a glutamate receptor that acts as a calcium channel. Activation of NMDAR induces actin rearrangement in cells of the central nervous system, but whether it helps maintain the epithelial phenotype of the proximal tubule is unknown. Here, knockdown of NMDAR1 in a proximal tubule cell line (HK-2) induced changes in cell morphology, reduced E-cadherin expression, and increased α-SMA expression. Induction of EMT with TGF-β1 led to downregulation of both E-cadherin and membrane-associated β-catenin, reorganization of F-actin, expression of mesenchymal markers de novo, upregulation of Snail1, and increased cell migration; co-treatment with NMDA attenuated all of these changes. Furthermore, NMDA reduced TGF-β1-induced phosphorylation of Erk1/2 and Akt and the activation of Ras, suggesting that NMDA antagonizes TGF-β1-induced EMT by inhibiting the Ras-MEK pathway. In the unilateral ureteral obstruction model, treatment with NMDA blunted obstruction-induced upregulation of α-SMA, FSP1, and collagen I and downregulation of E-cadherin. Taken together, these results suggest that NMDAR plays a critical role in preserving the normal epithelial phenotype and modulating tubular EMT.
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