ArticleJournal of cell science2010
Assembly of fibrillin microfibrils governs extracellular deposition of latent TGF beta.
Article in Journal of cell science, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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Who cites it
101 citing papers in PubMed, 162 citations in OpenAlex.
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- Losartan shows limited benefit in preclinical models of Geleophysic dysplasia.Scientific reports · 2026Article
- The hypoxic tight-skin mouse model of Group 3 pulmonary hypertension.Scientific reports · 2026Article
- Review
- TGFβ-dependent signaling drives tumor growth and aberrant extracellular matrix dynamics in NF1-associated plexiform neurofibroma.Science advances · 2025Article
- ECM formation and degradation during fibrosis, repair, and regeneration.npj metabolic health and disease · 2025Review
- The secreted protease ADAMTS18 is a novel activator of latent TGF-β to exacerbate renal fibrosis.Communications biology · 2025Article
- Dysregulation of cell migration by matrix metalloproteinases in geleophysic dysplasia.Scientific reports · 2025Article
- Collagen type VI regulates TGF-β bioavailability in skeletal muscle in mice.The Journal of clinical investigation · 2025Article
- Calcification of the elastic component: the impact on the cardiovascular system.Frontiers in cardiovascular medicine · 2025Review
- Silencing SPP1 in M2 macrophages inhibits the progression of castration-resistant prostate cancer via the MMP9/TGFβ1 axis.Translational andrology and urology · 2024Article
- Hitting the Target! Challenges and Opportunities for TGF-β Inhibition for the Treatment of Cardiac fibrosis.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Genetic models of fibrillinopathies.Genetics · 2024Review
- The extracellular matrix glycoprotein fibrillin-1 in health and disease.Frontiers in cell and developmental biology · 2023Review
- Mechanism of Extracellular Vesicle Secretion Associated with TGF-β-Dependent Inflammatory Response in the Tumor Microenvironment.International journal of molecular sciences · 2022Review
- The Fibrillin-1/VEGFR2/STAT2 signaling axis promotes chemoresistance via modulating glycolysis and angiogenesis in ovarian cancer organoids and cells.Cancer communications (London, England) · 2022Article
- Latent TGFβ complexes are transglutaminase cross-linked to fibrillin to facilitate TGFβ activation.Matrix biology : journal of the International Society for Matrix Biology · 2022Article
- Mechanical Cues: Bidirectional Reciprocity in the Extracellular Matrix Drives Mechano-Signalling in Articular Cartilage.International journal of molecular sciences · 2021Review
- The extracellular matrix glycoprotein ADAMTSL2 is increased in heart failure and inhibits TGFβ signalling in cardiac fibroblasts.Scientific reports · 2021Article
- POGLUT2 and POGLUT3 O-glucosylate multiple EGF repeats in fibrillin-1, -2, and LTBP1 and promote secretion of fibrillin-1.The Journal of biological chemistry · 2021Article
41 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Control of the bioavailability of the growth factor TGFbeta is essential for tissue formation and homeostasis, yet precisely how latent TGFbeta is incorporated into the extracellular matrix is unknown. Here, we show that deposition of a large latent TGFbeta complex (LLC), which contains latent TGFbeta-binding protein 1 (LTBP-1), is directly dependent on the pericellular assembly of fibrillin microfibrils, which interact with fibronectin during higher-order fibrillogenesis. LTBP-1 formed pericellular arrays that colocalized with microfibrils, whereas fibrillin knockdown inhibited fibrillar LTBP-1 and/or LLC deposition. Blocking alpha5beta1 integrin or supplementing cultures with heparin, which both inhibited microfibril assembly, disrupted LTBP-1 deposition and enhanced Smad2 phosphorylation. Full-length LTBP-1 bound only weakly to N-terminal pro-fibrillin-1, but this association was strongly enhanced by heparin. The microfibril-associated glycoprotein MAGP-1 (MFAP-2) inhibited LTBP-1 binding to fibrillin-1 and stimulated Smad2 phosphorylation. By contrast, fibulin-4, which interacted strongly with full-length LTBP-1, did not induce Smad2 phosphorylation. Thus, LTBP-1 and/or LLC deposition is dependent on pericellular microfibril assembly and is governed by complex interactions between LTBP-1, heparan sulfate, fibrillin-1 and microfibril-associated molecules. In this way, microfibrils control TGFbeta bioavailability.
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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.