ArticleProceedings of the National Academy of Sciences of the United States of America2019
Fibulin-4 exerts a dual role in LTBP-4L-mediated matrix assembly and function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Conserved hepatic RNA signatures across multiple cohorts reveal novel mechanistic clues for advanced fibrosis in human MASLD.Hepatology communications · 2026Pooled it
- Fibulin-4 expressed in metastatic breast cancer is a target of peptide-based imaging probes and experimental therapeutics.Molecular therapy. Oncology · 2026Article
- Impact of N-linked glycans on the dual short fibulin/LTBP-4 axes regulating elastogenesis.The FEBS journal · 2025Article
- Fibulin-1 deficiency alleviates liver fibrosis by inhibiting hepatic stellate cell activation via the p38 MAPK pathway.Cellular and molecular life sciences : CMLS · 2025Article
- Extracellular matrix in vascular homeostasis and disease.Nature reviews. Cardiology · 2025Review
- Fibulin-4 and latent-transforming growth factor beta-binding protein-4 interactions with syndecan-2 and syndecan-3 are required for elastogenesis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- M1 macrophages deliver CASC19 via exosomes to inhibit the proliferation and migration of colon cancer cells.Medical oncology (Northwood, London, England) · 2024Article
- Microfibril-associated glycoprotein 4 forms octamers that mediate interactions with elastogenic proteins and cells.Nature communications · 2024Article
- Protective Role of Endothelial Fibulin-4 in Valvulo-Arterial Integrity.Journal of the American Heart Association · 2023Article
- Fibrillin-1-regulated miR-122 has a critical role in thoracic aortic aneurysm formation.Cellular and molecular life sciences : CMLS · 2022Article
- Targeting TGF-β signal transduction for fibrosis and cancer therapy.Molecular cancer · 2022Review
- Elastic Fibre Proteins in Elastogenesis and Wound Healing.International journal of molecular sciences · 2022Review
- Physiologically relevant platform for an advanced in vitro model of the vascular wall: focus on in situ fabrication and mechanical maturation.In vitro models · 2022Article
- Annuloaortic ectasia in a four-month-old male Newfoundland dog: long-term follow-up and immunofluorescent study.The veterinary quarterly · 2021Article
- Structural studies of elastic fibre and microfibrillar proteins.Matrix biology plus · 2021Article
- Alveologenesis: What Governs Secondary Septa Formation.International journal of molecular sciences · 2021Review
- PAD2-mediated citrullination of Fibulin-5 promotes elastogenesis.Matrix biology : journal of the International Society for Matrix Biology · 2021Article
- An increase in elastogenic components in the placental villi of women with chronic venous disease during pregnancy is associated with decreased EGFL7 expression level.Molecular medicine reports · 2021Observational
- Bi-allelic premature truncating variants in LTBP1 cause cutis laxa syndrome.American journal of human genetics · 2021Article
- Autosomal Recessive Cutis Laxa 1C Mutations Disrupt the Structure and Interactions of Latent TGFβ Binding Protein-4.Frontiers in genetics · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Elastogenesis is a hierarchical process by which cells form functional elastic fibers, providing elasticity and the ability to regulate growth factor bioavailability in tissues, including blood vessels, lung, and skin. This process requires accessory proteins, including fibulin-4 and -5, and latent TGF binding protein (LTBP)-4. Our data demonstrate mechanisms in elastogenesis, focusing on the interaction and functional interdependence between fibulin-4 and LTBP-4L and its impact on matrix deposition and function. We show that LTBP-4L is not secreted in the expected extended structure based on its domain composition, but instead adopts a compact conformation. Interaction with fibulin-4 surprisingly induced a conformational switch from the compact to an elongated LTBP-4L structure. This conversion was only induced by fibulin-4 multimers associated with increased avidity for LTBP-4L; fibulin-4 monomers were inactive. The fibulin-4-induced conformational change caused functional consequences in LTBP-4L in terms of binding to other elastogenic proteins, including fibronectin and fibrillin-1, and of LTBP-4L assembly. A transient exposure of LTBP-4L with fibulin-4 was sufficient to stably induce conformational and functional changes; a stable complex was not required. These data define fibulin-4 as a molecular extracellular chaperone for LTBP-4L. The altered LTBP-4L conformation also promoted elastogenesis, but only in the presence of fibulin-4, which is required to escort tropoelastin onto the extended LTBP-4L molecule. Altogether, this study provides a dual mechanism for fibulin-4 in 1) inducing a stable conformational and functional change in LTBP-4L, and 2) promoting deposition of tropoelastin onto the elongated LTBP-4L.
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