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Updated: Jun 29, 2025
07:49
Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
Published on: August 3, 2018
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TGF-β1 Drives Integrin-Dependent Pericyte Migration and Microvascular Destabilization in Fibrotic Disease.
Amanda S Pellowe1, Michelle J Wu1, Tae-Yun Kang1
1Department of Biomedical Engineering, Yale University, New Haven, Connecticut.
The American Journal of Pathology
|March 28, 2024
Summary
Pericytes (PCs) migrate from blood vessels in fibrotic diseases, driven by transforming growth factor β1 (TGF-β1) and integrins. This migration destabilizes microvasculature, indicating early tissue fibrosis.
Area of Science:
- Cell biology
- Vascular biology
- Fibrosis research
Background:
- Endothelial cell (EC)-pericyte (PC) interactions are vital for microvascular stability.
- Dysfunctional EC-PC interactions characterize fibrotic diseases like systemic sclerosis.
- The role of PCs in microvascular signaling and dysfunction is not fully understood.
Purpose of the Study:
- To investigate how integrin-matrix interactions influence PC migration and myofibroblast conversion.
- To determine the effects of pro-inflammatory (TNFα) and fibrotic (TGF-β1) factors on PC phenotypes.
- To assess the impact of PC changes on endothelial dysfunction and vascular stability.
Main Methods:
- Human PCs were treated with TNFα or TGF-β1.
- Assessed PC migration, matrix deposition, and integrin expression.
- Measured EC angiopoietin-2 levels as a marker of vascular instability.
- Examined systemic sclerosis patient skin for vascular stability changes.
Main Results:
- Both TNFα and TGF-β1 altered PC integrin expression and matrix deposition.
- TGF-β1 induced PC migration in an integrin-dependent manner.
- PC migration correlated with increased EC angiopoietin-2 levels, indicating vascular instability.
- Systemic sclerosis skin showed altered vascular stability.
Conclusions:
- TNFα and TGF-β1 modify PC integrin expression and matrix deposition, promoting migration.
- Integrin-dependent PC migration destabilizes microvasculature.
- Microvascular destabilization may serve as an early indicator of tissue fibrosis.
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