ArticleScientific reports2015
Fibulin-4 deficiency increases TGF-β signalling in aortic smooth muscle cells due to elevated TGF-β2 levels.
Article in Scientific reports, 2015. 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, 29 citations in OpenAlex.
- Heterochronic activation of TGF-β signaling drives the diversity of the avian sterna.Nature communications · 2026Article
- Modeling Thoracic Aortic Dissection Using Patient-Specific iPSCs Reveals VSMC Dysfunction and Extracellular Matrix Dysregulation.Stem cells international · 2025Article
- Matricellular proteins in immunometabolism and tissue homeostasis.BMB reports · 2024Review
- Increased vascular smooth muscle cell senescence in aneurysmal Fibulin-4 mutant mice.npj aging · 2024Article
- Review
- Dysregulations of Key Regulators of Angiogenesis and Inflammation in Abdominal Aortic Aneurysm.International journal of molecular sciences · 2023Article
- Acute Elution of TGFβ2 Affects the Smooth Muscle Cells in a Compliance-Matched Vascular Graft.Tissue engineering. Part A · 2022Article
- Elastic Fibre Proteins in Elastogenesis and Wound Healing.International journal of molecular sciences · 2022Review
- Molecular Imaging of Aortic Aneurysm and Its Translational Power for Clinical Risk Assessment.Frontiers in medicine · 2022Review
- Transforming Growth Factor-β and the Renin-Angiotensin System in Syndromic Thoracic Aortic Aneurysms: Implications for Treatment.Cardiovascular drugs and therapy · 2021Review
- Deletion of AT1a (Angiotensin II Type 1a) Receptor or Inhibition of Angiotensinogen Synthesis Attenuates Thoracic Aortopathies in Fibrillin1Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Modulating smooth muscle cell response by the release of TGFβ2 from tubular scaffolds for vascular tissue engineering.Journal of controlled release : official journal of the Controlled Release Society · 2019Article
- Decreased mitochondrial respiration in aneurysmal aortas of Fibulin-4 mutant mice is linked to PGC1A regulation.Cardiovascular research · 2018Article
- Extracellular Interactions between Fibulins and Transforming Growth Factor (TGF)-β in Physiological and Pathological Conditions.International journal of molecular sciences · 2018Review
- Identification of new regulators of embryonic patterning and morphogenesis in Xenopus gastrulae by RNA sequencing.Developmental biology · 2017Article
- Fluid shear stress-induced TGF-β/ALK5 signaling in renal epithelial cells is modulated by MEK1/2.Cellular and molecular life sciences : CMLS · 2017Article
- Fibulin-4 is essential for maintaining arterial wall integrity in conduit but not muscular arteries.Science advances · 2017Article
- Thoracic Aortic Aneurysm Development in Patients with Bicuspid Aortic Valve: What Is the Role of Endothelial Cells?Frontiers in physiology · 2017Review
- Defective Connective Tissue Remodeling in Smad3 Mice Leads to Accelerated Aneurysmal Growth Through Disturbed Downstream TGF-β Signaling.EBioMedicine · 2016Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fibulins are extracellular matrix proteins associated with elastic fibres. Homozygous Fibulin-4 mutations lead to life-threatening abnormalities such as aortic aneurysms. Aortic aneurysms in Fibulin-4 mutant mice were associated with upregulation of TGF-β signalling. How Fibulin-4 deficiency leads to deregulation of the TGF-β pathway is largely unknown. Isolated aortic smooth muscle cells (SMCs) from Fibulin-4 deficient mice showed reduced growth, which could be reversed by treatment with TGF-β neutralizing antibodies. In Fibulin-4 deficient SMCs increased TGF-β signalling was detected using a transcriptional reporter assay and by increased SMAD2 phosphorylation. Next, we investigated if the increased activity was due to increased levels of the three TGF-β isoforms. These data revealed slightly increased TGF-β1 and markedly increased TGF-β2 levels. Significantly increased TGF-β2 levels were also detectable in plasma from homozygous Fibulin-4(R/R) mice, not in wild type mice. TGF-β2 levels were reduced after losartan treatment, an angiotensin-II type-1 receptor blocker, known to prevent aortic aneurysm formation. In conclusion, we have shown increased TGF-β signalling in isolated SMCs from Fibulin-4 deficient mouse aortas, not only caused by increased levels of TGF-β1, but especially TGF-β2. These data provide new insights in the molecular interaction between Fibulin-4 and TGF-β pathway regulation in the pathogenesis of aortic aneurysms.
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