ArticleThe Journal of clinical investigation2022
Loss of the collagen IV modifier prolyl 3-hydroxylase 2 causes thin basement membrane nephropathy.
Article in The Journal of clinical investigation, 2022. 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, 32 citations in OpenAlex.
- Update on Alport Syndrome: The Report of the 2024 International Workshop on Alport Syndrome.Kidney international reports · 2026Article
- Identification of COL4A2 as a Biomarker of Extracellular Matrix Remodeling and Vascular Scaffold in Choroid for Myopia.Investigative ophthalmology & visual science · 2026Article
- Evidence for the major role of PH4⍺EFB in the prolyl 4-hydroxylation of Drosophila collagen IV.Matrix biology : journal of the International Society for Matrix Biology · 2025Article
- Collagen IV in Gould syndrome and Alport syndrome.Nature reviews. Nephrology · 2025Review
- Collagen IV biosynthesis: Intracellular choreography of post-translational modifications.Matrix biology : journal of the International Society for Matrix Biology · 2025Review
- The Life of a Kidney Podocyte.Acta physiologica (Oxford, England) · 2025Review
- The life cycle of type IV collagen.Matrix biology : journal of the International Society for Matrix Biology · 2025Review
- Genetics and Clinical Findings Associated with Early-Onset Myopia and Retinal Detachment in Saudi Arabia.Genes · 2025Review
- Methylseq, single-nuclei RNAseq, and discovery proteomics identify pathways associated with nephron-deficit CKD in the HSRA rat model.American journal of physiology. Renal physiology · 2025Article
- Nephrotic-range proteinuria in a 53-year-old female with thin basement membrane nephropathy: A case report with literature review.SAGE open medical case reports · 2025Article
- Early Diagnosis and Treatment of Kidney Injury: A Focus on Urine Protein.International journal of molecular sciences · 2024Review
- Single-cell transcriptome atlas in C57BL/6 mice encodes morphological phenotypes in the aging kidneys.BMC nephrology · 2024Article
- The proteasome modulates endocytosis specifically in glomerular cells to promote kidney filtration.Nature communications · 2024Article
- PolyAMiner-Bulk is a deep learning-based algorithm that decodes alternative polyadenylation dynamics from bulk RNA-seq data.Cell reports methods · 2024Article
- Collagen IV of basement membranes: II. Emergence of collagen IVThe Journal of biological chemistry · 2023Article
- Review
- Expansion-enhanced super-resolution radial fluctuations enable nanoscale molecular profiling of pathology specimens.Nature nanotechnology · 2023Article
- Article
- A Comparative Presentation of Mouse Models That Recapitulate Most Features of Alport Syndrome.Genes · 2022Review
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Authors and funding
22 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The glomerular filtration barrier (GFB) produces primary urine and is composed of a fenestrated endothelium, a glomerular basement membrane (GBM), podocytes, and a slit diaphragm. Impairment of the GFB leads to albuminuria and microhematuria. The GBM is generated via secreted proteins from both endothelial cells and podocytes and is supposed to majorly contribute to filtration selectivity. While genetic mutations or variations of GBM components have been recently proposed to be a common cause of glomerular diseases, pathways modifying and stabilizing the GBM remain incompletely understood. Here, we identified prolyl 3-hydroxylase 2 (P3H2) as a regulator of the GBM in an a cohort of patients with albuminuria. P3H2 hydroxylates the 3' of prolines in collagen IV subchains in the endoplasmic reticulum. Characterization of a P3h2ΔPod mouse line revealed that the absence of P3H2 protein in podocytes induced a thin basement membrane nephropathy (TBMN) phenotype with a thinner GBM than that in WT mice and the development of microhematuria and microalbuminuria over time. Mechanistically, differential quantitative proteomics of the GBM identified a significant decrease in the abundance of collagen IV subchains and their interaction partners in P3h2ΔPod mice. To our knowledge, P3H2 protein is the first identified GBM modifier, and loss or mutation of P3H2 causes TBMN and focal segmental glomerulosclerosis in mice and humans.
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