ArticleThe Journal of clinical investigation2019
uPAR isoform 2 forms a dimer and induces severe kidney disease in mice.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Increased soluble urokinase plasminogen activator levels modulate monocyte function to promote atherosclerosis.The Journal of clinical investigation · 2022Pooled it
- Inflammatory Markers and Measures of Cardiovascular Autonomic Neuropathy in Type 1 Diabetes.Journal of the American Heart Association · 2025Trial
- An inducible co-stimulator ligand (ICOSL)-based peptide therapy for proteinuric kidney diseases targeting αvβ3 integrin.Molecular biomedicine · 2026Article
- uPAR/suPAR Signaling and Organ Crosstalk in Cardiovascular-Kidney-Metabolic Syndrome.Circulation research · 2026Review
- From heart to kidney: FGF23, SuPAR, and NAG as early biomarkers of cardiorenal syndrome in acute heart failure.BMC cardiovascular disorders · 2026Observational
- Endothelial cell-released CD93 contributes to podocyte injury in idiopathic nephrotic syndrome.Science translational medicine · 2026Article
- The role of suPAR and related proteins in kidney, heart diseases, and diabetes.The Journal of clinical investigation · 2026Review
- Associations of Biomarkers of Kidney Tubule Health with Retinal Microvascular Signs: The Multi-Ethnic Study of Atherosclerosis.Kidney360 · 2025Article
- Review
- Pathogenesis of Focal Segmental Glomerulosclerosis and Related Disorders.Annual review of pathology · 2025Review
- Clinical value of soluble urokinase-type plasminogen activator receptor in predicting sepsis-associated acute kidney injury.Renal failure · 2024Article
- Obesity, Inflammation, and Clinical Outcomes in COVID-19: A Multicenter Prospective Cohort Study.The Journal of clinical endocrinology and metabolism · 2024Observational
- STAT3-mediated up-regulation of DAB2 via SRC-YAP1 signaling axis promotes Helicobacter pylori-driven gastric tumorigenesis.Biomarker research · 2024Article
- Nomogram Model for Cardiac Surgery-Associated Acute Kidney Injury Based on Clinical Characteristics Combined with Plasma suPAR.International journal of general medicine · 2024Article
- Role of Soluble Urokinase-Type Plasminogen Activator Receptor in Cardiovascular Disease.Current cardiology reports · 2023Review
- Prospective Cohort Study of Soluble Urokinase Plasminogen Activation Receptor and Cardiovascular Events in Patients With CKD.Kidney international reports · 2023Article
- Article
- SuPAR mediates viral response proteinuria by rapidly changing podocyte function.Nature communications · 2023Article
- Recent Advances in Proteinuric Kidney Disease/Nephrotic Syndrome: Lessons from Knockout/Transgenic Mouse Models.Biomedicines · 2023Review
- suPAR links a dysregulated immune response to tissue inflammation and sepsis-induced acute kidney injury.JCI insight · 2023Article
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Authors and funding
24 authors at 5 institutions in 1 country.
Funding
Abstract
Soluble urokinase plasminogen activator receptor (suPAR) is an immune-derived circulating signaling molecule that has been implicated in chronic kidney disease, such as focal segmental glomerulosclerosis (FSGS). Typically, native uPAR (isoform 1) translates to a 3-domain protein capable of binding and activating integrins, yet the function of additional isoforms generated by alternative splicing is unknown. Here, we characterized mouse uPAR isoform 2 (msuPAR2), encoding domain I and nearly one-half of domain II, as a dimer in solution, as revealed by 3D electron microscopy structural analysis. In vivo, msuPAR2 transgenic mice exhibited signs of severe renal disease characteristic of FSGS with proteinuria, loss of kidney function, and glomerulosclerosis. Sequencing of the glomerular RNAs from msuPAR2-Tg mice revealed a differentially expressed gene signature that includes upregulation of the suPAR receptor Itgb3, encoding β3 integrin. Crossing msuPAR2-transgenic mice with 3 different integrin β3 deficiency models rescued msuPAR2-mediated kidney function. Further analyses indicated a central role for β3 integrin and c-Src in msuPAR2 signaling and in human FSGS kidney biopsies. Administration of Src inhibitors reduced proteinuria in msuPAR2-transgenic mice. In conclusion, msuPAR2 may play an important role in certain forms of scarring kidney disease.
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Registered trials
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.