ArticleBiochimica et biophysica acta. Molecular basis of disease2021
RAGE and αVβ3-integrin are essential for suPAR signaling in podocytes.
Article in Biochimica et biophysica acta. Molecular basis of disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 17 citations in OpenAlex.
- suPAR Identifies Treatment-Resistant Inflammatory Risk Beyond hs-CRP in Type 2 Diabetes With Coronary Artery Disease: An Ancillary Analysis of BARI 2D.Diabetes care · 2026Trial
- An inducible co-stimulator ligand (ICOSL)-based peptide therapy for proteinuric kidney diseases targeting αvβ3 integrin.Molecular biomedicine · 2026Article
- The ELAVL1-PLAUR-suPAR Axis Exacerbates Diabetic Nephropathy by Promoting Podocyte Injury and Inflammation.Journal of diabetes · 2026Article
- uPAR/suPAR Signaling and Organ Crosstalk in Cardiovascular-Kidney-Metabolic Syndrome.Circulation research · 2026Review
- Chromatin dynamics identifies 78 genes at loci associated with elevated intraocular pressure and primary open-angle glaucoma.bioRxiv : the preprint server for biology · 2026Article
- Advances in Targeting the AGEs-RAGE Pathway for the Treatment of Diabetic Kidney Disease.Drug design, development and therapy · 2026Review
- Modulation of Aging Diseases via RAGE Targets: A Dietary Intervention Review.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Soluble urokinase plasminogen activator receptor promotes endoplasmic reticulum stress and apoptosis susceptibility through RAGE in sepsis acute kidney injury.Molecular medicine (Cambridge, Mass.) · 2025Article
- The Advanced Glycation End-Products (AGE)-Receptor for AGE System (RAGE): An Inflammatory Pathway Linking Obesity and Cardiovascular Diseases.International journal of molecular sciences · 2025Review
- Advances in the diagnosis of early biomarkers for acute kidney injury: a literature review.BMC nephrology · 2025Review
- Article
- Cellular crosstalk of mesangial cells and tubular epithelial cells in diabetic kidney disease.Cell communication and signaling : CCS · 2023Review
- Periostin C-Terminal Is Intrinsically Disordered and Interacts with 143 Proteins in an In Vitro Epidermal Model of Atopic Dermatitis.Biochemistry · 2023Article
- Transient Receptor Potential Canonical 6 (TRPC6) Channel in the Pathogenesis of Diseases: A Jack of Many Trades.Inflammation · 2023Review
- Ion channels and channelopathies in glomeruli.Physiological reviews · 2023Review
- Molecular Mechanisms of Kidney Injury and Repair.International journal of molecular sciences · 2022Review
- suPAR to Risk-Stratify Patients With Malaria.Frontiers in immunology · 2022Review
- Decoding the Mechanism behind the Pathogenesis of the Focal Segmental Glomerulosclerosis.Computational and mathematical methods in medicine · 2022Article
- RAGE pathway activation and function in chronic kidney disease and COVID-19.Frontiers in medicine · 2022Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The soluble urokinase plasminogen activator receptor (suPAR) has been implicated in the pathogenesis of kidney diseases including primary and recurrent focal and segmental glomerulosclerosis (FSGS), diabetic nephropathy, and acute kidney injuries (AKI). Elevated serum suPAR concentration is a negative prognostic indicator in multiple critical clinical conditions. This study has examined the initial transduction steps used by suPAR in cultured mouse podocytes. We now report that the receptor for advanced glycation end-products (RAGE) co-immunoprecipitates with αV and β3 integrin subunits, which have been previously shown to initiate suPAR signal transduction at the podocyte cell surface. siRNA knock-down of RAGE attenuated Src phosphorylation evoked by either suPAR or by glycated albumin (AGE-BSA), a prototypical RAGE agonist. suPAR effects on Src phosphorylation were also blocked by the structurally dissimilar RAGE antagonists FPS-ZM1 and azeliragon, as well as by cilengitide, an inhibitor of outside-in signaling through αV-integrins. FPS-ZM1 also blocked Src phosphorylation evoked by AGE-BSA. FPS-ZM1 blocked increases in cell surface TRPC6 abundance, cytosolic reactive oxygen species (ROS) and activation of the small GTPase Rac1 evoked by either suPAR or AGE-BSA. In addition, FPS-ZM1 inhibited Src phosphorylation evoked by serum collected from a patient with recurrent FSGS during a relapse. The magnitude of this inhibition was indistinguishable from the effect produced by a neutralizing antibody against suPAR. These data suggest that orally bioavailable small molecule RAGE antagonists could represent a useful therapeutic strategy for a wide range of clinical conditions associated with elevated serum suPAR, including primary FSGS and AKI.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.