ArticleThe Journal of clinical investigation2012
Gain of glycosylation in integrin α3 causes lung disease and nephrotic syndrome.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 128 citations in OpenAlex.
- Expanding the phenotypic spectrum of ILNEB: Absence of classic dermatologic findings in a 12-year-old girl with homozygous ITGA3 p.Arg274Gln.JAAD case reports · 2026Article
- Dysregulated ITGA3/FAK/YAP axis mediates impaired alveolar type II epithelial cells function in COPD.Journal of advanced research · 2026Article
- Laminin Receptors in Peripheral Tissues: Functions Revealed by Analysis of Knockout Mice.The American journal of pathology · 2025Review
- Review
- Nephronectin (NPNT) is a Crucial Determinant of Idiopathic Pulmonary Fibrosis: Modulating Cellular Senescence via the ITGA3/YAP1 Signaling Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Integrins in the kidney - beyond the matrix.Nature reviews. Nephrology · 2025Review
- The epidermal integrin-mediated secretome regulates the skin microenvironment during tumorigenesis and repair.Matrix biology : journal of the International Society for Matrix Biology · 2024Review
- Integrin mutations in blistering skin diseases and related genetically engineered mouse models.Human immunology · 2024Review
- Sialyl Lewis X decorated integrin α3 on small extracellular vesicles promotes metastasis of bladder cancer via enhancing vascular permeability.Angiogenesis · 2024Article
- Minimal Change Disease: Pathogenetic Insights from Glomerular Proteomics.International journal of molecular sciences · 2024Article
- Roles for epithelial integrin α3β1 in regulation of the microenvironment during normal and pathological tissue remodeling.American journal of physiology. Cell physiology · 2024Review
- Metabolism-driven glycosylation represents therapeutic opportunities in interstitial lung diseases.Frontiers in immunology · 2024Review
- Integrin α3 mutation junctional epidermolysis bullosa presenting with hypotrichosis and lacrimal obstruction.JAAD case reports · 2024Article
- Conditional knockout of ITGB4 in bronchial epithelial cells directs bronchopulmonary dysplasia.Journal of cellular and molecular medicine · 2023Article
- Article
- Inhibition of DPAGT1 suppresses HER2 shedding and trastuzumab resistance in human breast cancer.The Journal of clinical investigation · 2023Article
- Nephrotic syndrome, skin involvement, and chronic lung disease: Answers.Pediatric nephrology (Berlin, Germany) · 2023Article
- Targeting protein glycosylation to regulate inflammation in the respiratory tract: novel diagnostic and therapeutic candidates for chronic respiratory diseases.Frontiers in immunology · 2023Review
- Integrin α3 negative podocytes: A gene expression study.Matrix biology plus · 2022Article
4 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Integrins are transmembrane αβ glycoproteins that connect the extracellular matrix to the cytoskeleton. The laminin-binding integrin α3β1 is expressed at high levels in lung epithelium and in kidney podocytes. In podocytes, α3β1 associates with the tetraspanin CD151 to maintain a functional filtration barrier. Here, we report on a patient homozygous for a novel missense mutation in the human ITGA3 gene, causing fatal interstitial lung disease and congenital nephrotic syndrome. The mutation caused an alanine-to-serine substitution in the integrin α3 subunit, thereby introducing an N-glycosylation motif at amino acid position 349. We expressed this mutant form of ITGA3 in murine podocytes and found that hyperglycosylation of the α3 precursor prevented its heterodimerization with β1, whereas CD151 association with the α3 subunit occurred normally. Consequently, the β1 precursor accumulated in the ER, and the mutant α3 precursor was degraded by the ubiquitin-proteasome system. Thus, these findings uncover a gain-of-glycosylation mutation in ITGA3 that prevents the biosynthesis of functional α3β1, causing a fatal multiorgan disorder.
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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.