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Flow-induced HDAC1 phosphorylation and nuclear export in angiogenic sprouting
Despina Bazou1, Mei Rosa Ng1, Jonathan W Song2
1Edwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, 100 Blossom Street, Boston, Massachusetts 02114, USA.
Scientific Reports
|September 28, 2016
Summary
Endothelial morphogenesis during angiogenesis is regulated by histone deacetylase-1 (HDAC1). Interstitial flow enhances HDAC1 activity, promoting cell migration and vascularization, offering a new therapeutic target.
Area of Science:
- Cell Biology
- Biochemistry
- Physiology
Background:
- Angiogenesis involves endothelial cell (EC) growth and migration, influenced by signals like vascular endothelial growth factor (VEGF) and mechanical stimuli.
- Interstitial flow, a mechanical stimulus, is elevated in tumor microenvironments, but its interaction with VEGF signaling in angiogenesis is unclear.
Purpose of the Study:
- To investigate the role of histone deacetylase-1 (HDAC1) in endothelial morphogenesis.
- To determine how interstitial flow affects HDAC1 activity and its impact on angiogenesis.
Main Methods:
- Studied endothelial cell (EC) morphogenesis in response to interstitial flow.
- Assessed histone deacetylase-1 (HDAC1) phosphorylation, nuclear export, and activity.
- Investigated the effect of HDAC1 inhibition on EC morphogenesis and matrix metalloproteinase-14 (MMP14) expression.
Main Results:
- Endothelial morphogenesis is dependent on histone deacetylase-1 (HDAC1).
- Interstitial flow increases HDAC1 phosphorylation, activity, and nuclear export.
- HDAC1 inhibition reduces endothelial morphogenesis and matrix metalloproteinase-14 (MMP14) expression.
Conclusions:
- Histone deacetylase-1 (HDAC1) plays a crucial role in modulating angiogenesis in response to interstitial flow.
- HDAC1 is a potential therapeutic target for controlling vascularization in clinical settings.
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