ArticleKidney international2016
Endothelin A receptor activation on mesangial cells initiates Alport glomerular disease.
Article in Kidney international, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Potential Renal Damage Biomarkers in Alport Syndrome-A Review of the Literature.International journal of molecular sciences · 2022Pooled it
- New therapeutic hope for rare podocytopathies.Pediatric nephrology (Berlin, Germany) · 2026Review
- Podocyte-derived endothelin-1 and endothelial cell endothelin A receptors are essential for glomerular injury in mouse models of focal segmental glomerulosclerosis.Kidney international · 2026Article
- Treatment Approaches for Alport Syndrome.Journal of the American Society of Nephrology : JASN · 2026Review
- CKDs at the Crossroads: From Failures to Future Therapies.Kidney international reports · 2025Review
- Research trends and performance of endothelin A receptor antagonist in kidney care: a bibliometric analysis.Renal failure · 2025Article
- The role of endothelin receptor antagonists in kidney disease.Renal failure · 2025Review
- Collagen IV in Gould syndrome and Alport syndrome.Nature reviews. Nephrology · 2025Review
- Genotype-Based Molecular Mechanisms in Alport Syndrome.Journal of the American Society of Nephrology : JASN · 2025Review
- Endothelin receptor antagonists in chronic kidney disease.Nature reviews. Nephrology · 2025Review
- Selective endothelin A receptor antagonism in chronic kidney disease: improving clinical application.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- Biomarkers for the early diagnosis of Alport syndrome and associated kidney damage.Childhood kidney diseases · 2025Review
- A Pilot Study on Protective Effect of Ambrisentan on Proteinuria in Patients With Alport Syndrome.Kidney international reports · 2024Article
- Role of the Innate Immune Response in Glomerular Disease Pathogenesis: Focus on Podocytes.Cells · 2024Review
- Mechanism of protective actions of sparsentan in the kidney: lessons from studies in models of chronic kidney disease.Clinical science (London, England : 1979) · 2024Review
- Ramipril therapy in integrin α1-null, autosomal recessive Alport mice triples lifespan: mechanistic clues from RNA-seq analysis.The Journal of pathology · 2024Article
- Dual inhibition of the endothelin and angiotensin receptor ameliorates renal and inner ear pathologies in Alport mice.The Journal of pathology · 2023Article
- Alport Syndrome: Clinical Spectrum and Therapeutic Advances.Kidney medicine · 2023Review
- Case of hereditary kidney disease presenting thin basement membrane with a single heterozygous variant of Intersectin 2.Journal of rural medicine : JRM · 2023Article
- Glomerular basement membrane deposition of collagen α1(III) in Alport glomeruli by mesangial filopodia injures podocytes via aberrant signaling through DDR1 and integrin α2β1.The Journal of pathology · 2022Article
Corrections and comments
- Commented on by
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Recent work demonstrates that Alport glomerular disease is mediated through a biomechanical strain-sensitive activation of mesangial actin dynamics. This occurs through a Rac1/CDC42 cross-talk mechanism that results in the invasion of the subcapillary spaces by mesangial filopodia. The filopodia deposit mesangial matrix proteins in the glomerular basement membrane, including laminin 211, which activates focal adhesion kinase in podocytes culminating in the up-regulation of proinflammatory cytokines and metalloproteinases. These events drive the progression of glomerulonephritis. Here we test whether endothelial cell-derived endothelin-1 is up-regulated in Alport glomeruli and further elevated by hypertension. Treatment of cultured mesangial cells with endothelin-1 activates the formation of drebrin-positive actin microspikes. These microspikes do not form when cells are treated with the endothelin A receptor antagonist sitaxentan or under conditions of small, interfering RNA knockdown of endothelin A receptor mRNA. Treatment of Alport mice with sitaxentan results in delayed onset of proteinuria, normalized glomerular basement membrane morphology, inhibition of mesangial filopodial invasion of the glomerular capillaries, normalization of glomerular expression of metalloproteinases and proinflammatory cytokines, increased life span, and prevention of glomerulosclerosis and interstitial fibrosis. Thus endothelin A receptor activation on mesangial cells is a key event in initiation of Alport glomerular disease in this model.
Indexed as
Identifiers
What OpenQuestion holds
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.