PXD024162 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Thymosin 4 protects against aortic aneurysm via endocytic regulation of growth factor signalling |
Description | Vascular stability and tone are maintained by contractile smooth muscle cells (VSMCs). However, injury-induced growth factors stimulate a contractile-synthetic phenotypic modulation which increases susceptibility to abdominal aortic aneurysm (AAA). As a regulator of embryonic VSMC differentiation, we hypothesised that Thymosin β4 (Tβ4) may function to maintain healthy vasculature throughout postnatal life. This was supported by the identification of an interaction with Low density lipoprotein receptor related protein 1 (LRP1), an endocytic regulator of PDGF-BB signalling and VSMC proliferation. LRP1 variants have been implicated by genome-wide association studies with risk of AAA and other arterial diseases. T4-null mice displayed aortic VSMC and elastin defects, phenocopying LRP1 mutants, and their compromised vascular integrity predisposed to Angiotensin II-induced aneurysm formation. Aneurysmal vessels were characterised by enhanced VSMC phenotypic modulation and augmented platelet-derived growth factor (PDGF) receptor (PDGFR)β signalling. In vitro, enhanced sensitivity to PDGF-BB, upon loss of Tβ4, associated with dysregulated endocytosis, with increased recycling and reduced lysosomal targeting of LRP1-PDGFRβ. Accordingly, the exacerbated aneurysmal phenotype in T4-null mice was rescued upon treatment with the PDGFRβ antagonist, Imatinib. Our study identifies Tβ4 as a key regulator of LRP1 for maintaining vascular health and provides insights into the mechanisms of growth factor-controlled VSMC phenotypic modulation underlying aortic disease progression. |
HostingRepository | PRIDE |
AnnounceDate | 2021-05-21 |
AnnouncementXML | Submission_2021-05-21_05:14:21.678.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Svenja Hester |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-02-12 06:07:45 | ID requested | |
⏵ 1 | 2021-05-21 05:14:22 | announced | |
2 | 2023-11-14 08:51:58 | announced | 2023-11-14: Updated project metadata. |
Publication List
Keyword List
submitter keyword: Vascular stability,smooth muscle cells ,abdominal aortic aneurysm, Thymosin β4 , LRP1LRP1 , PDGFR)β signalling, endocytosis, |
Contact List
Professor Roman Fischer |
contact affiliation | University of Oxford, Nuffield Department of Medicine, Centre for Medicines Discovery |
contact email | roman.fischer@ndm.ox.ac.uk |
lab head | |
Svenja Hester |
contact affiliation | Nuffield Department of Medicine |
contact email | svenja.hester@ndm.ox.ac.uk |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD024162
- Label: PRIDE project
- Name: Thymosin 4 protects against aortic aneurysm via endocytic regulation of growth factor signalling