ArticleJournal of the American Society of Nephrology : JASN2014
Evidence for activation of the unfolded protein response in collagen IV nephropathies.
Article in Journal of the American Society of Nephrology : JASN, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 87 citations in OpenAlex.
- COL12A1 rs970547 Polymorphism Predisposes Anterior Cruciate Ligament Injury by Inducing ER Stress and Impairing Fibroblast Function.Advanced biology · 2026Article
- Genetic heterogeneity correlated with phenotypic variability in 6 Chinese families with Alport syndrome.Frontiers in genetics · 2026Article
- Minnelide ameliorates Col4a5+/- mice by upregulating Col4a5 and alleviating endoplasmic reticulum stress.Frontiers in pharmacology · 2026Article
- Treatment Approaches for Alport Syndrome.Journal of the American Society of Nephrology : JASN · 2026Review
- Collagen IV in Gould syndrome and Alport syndrome.Nature reviews. Nephrology · 2025Review
- Age at disease onset and risk of chronic kidney disease in patients with heterozygous disease-causing variants inClinical kidney journal · 2025Article
- Association of PLCE1 (rs7922612) and COL4A3 (rs375290088) Genetic Variants with the Risk of Nephrotic Syndrome in Egyptian Pediatric Patients.Biochemical genetics · 2025Article
- Genotype-Based Molecular Mechanisms in Alport Syndrome.Journal of the American Society of Nephrology : JASN · 2025Review
- The chemical chaperone 4-phenylbutyric acid rescues molecular cell defects of COL3A1 mutations that cause vascular Ehlers Danlos Syndrome.Cell death discovery · 2025Article
- Effects of a Novel COL4A3 Homozygous/Heterozygous Splicing Mutation on the Mild Phenotype in a Family With Autosomal Recessive Alport Syndrome and a Literature Review.Molecular genetics & genomic medicine · 2025Review
- Targeting endoplasmic reticulum stress: an innovative therapeutic strategy for podocyte-related kidney diseases.Journal of translational medicine · 2025Review
- Tauroursodeoxycholic acid ameliorates renal injury induced by COL4A3 mutation.Kidney international · 2024Article
- Exploration of Gene Therapy for Alport Syndrome.Biomedicines · 2024Review
- Progress in therapeutic targets on podocyte for Alport syndrome.Journal of translational internal medicine · 2024Article
- The spatially resolved transcriptome signatures of glomeruli in chronic kidney disease.JCI insight · 2024Article
- COL4A3 Mutation Induced Podocyte Apoptosis by Dysregulation of NADPH Oxidase 4 and MMP-2.Kidney international reports · 2023Article
- Research progress on endoplasmic reticulum homeostasis in kidney diseases.Cell death & disease · 2023Review
- Patient-derived podocyte spheroids reveal new insights into the etiopathogenesis of Alport syndrome.Frontiers in cell and developmental biology · 2023Article
- A Comparative Presentation of Mouse Models That Recapitulate Most Features of Alport Syndrome.Genes · 2022Review
- 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
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Authors and funding
19 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thin-basement-membrane nephropathy (TBMN) and Alport syndrome (AS) are progressive collagen IV nephropathies caused by mutations in COL4A3/A4/A5 genes. These nephropathies invariably present with microscopic hematuria and frequently progress to proteinuria and CKD or ESRD during long-term follow-up. Nonetheless, the exact molecular mechanisms by which these mutations exert their deleterious effects on the glomerulus remain elusive. We hypothesized that defective trafficking of the COL4A3 chain causes a strong intracellular effect on the cell responsible for COL4A3 expression, the podocyte. To this end, we overexpressed normal and mutant COL4A3 chains (G1334E mutation) in human undifferentiated podocytes and tested their effects in various intracellular pathways using a microarray approach. COL4A3 overexpression in the podocyte caused chain retention in the endoplasmic reticulum (ER) that was associated with activation of unfolded protein response (UPR)-related markers of ER stress. Notably, the overexpression of normal or mutant COL4A3 chains differentially activated the UPR pathway. Similar results were observed in a novel knockin mouse carrying the Col4a3-G1332E mutation, which produced a phenotype consistent with AS, and in biopsy specimens from patients with TBMN carrying a heterozygous COL4A3-G1334E mutation. These results suggest that ER stress arising from defective localization of collagen IV chains in human podocytes contributes to the pathogenesis of TBMN and AS through activation of the UPR, a finding that may pave the way for novel therapeutic interventions for a variety of collagenopathies.
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