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A PPARγ-dependent miR-424/503-CD40 axis regulates inflammation mediated angiogenesis
Aram Lee1, Irinna Papangeli2, Youngsook Park1
1Department of Life Systems, Sookmyung Women's University, 52 Hyochangwon-gil, Yongsan-gu, Seoul, 140-742, Korea.
Scientific Reports
|June 2, 2017
Summary
Researchers discovered a new pathway involving microRNAs (miR-424/503) that controls CD40 expression in endothelial cells, impacting inflammation and blood vessel growth. This finding sheds light on vascular disease mechanisms.
Area of Science:
- Endothelial cell biology
- Molecular mechanisms of vascular disease
- Inflammation and angiogenesis signaling
Background:
- Endothelial activation by inflammation drives vascular diseases.
- CD40/CD40 ligand signaling in endothelial cells is key to vascular inflammation.
- The precise molecular regulation of this pathway, especially concerning angiogenesis, remains unclear.
Purpose of the Study:
- To investigate the role of microRNAs in regulating endothelial CD40 expression.
- To elucidate the molecular mechanisms linking inflammation, CD40, and angiogenesis.
- To identify novel therapeutic targets for inflammatory vascular diseases.
Main Methods:
- Identified miR-424 and miR-503 as direct regulators of endothelial CD40 expression by targeting its 3' UTR.
- Assessed the impact of miR-424/503 on endothelial cell sprouting, migration, and tube formation in response to pro-inflammatory stimuli (LPS).
- Investigated the regulation of miR-424/503 by peroxisome proliferator-activated receptor gamma (PPARγ).
- Utilized a Matrigel plug assay in mice with endothelial-specific deletion of miR-322 (miR-424 ortholog) and miR-503 to study in vivo angiogenic response.
Main Results:
- miR-424 and miR-503 directly suppress endothelial CD40 expression.
- Pro-inflammatory stimuli decrease miR-424/503, leading to increased CD40 expression.
- miR-424/503 inhibit LPS-induced endothelial cell sprouting, migration, and tube formation.
- PPARγ directly regulates miR-424/503 expression, and its activity is reduced by inflammation.
- Mice lacking endothelial miR-322/miR-503 show enhanced angiogenic responses to LPS.
Conclusions:
- A novel PPARγ-dependent signaling axis involving miR-424/503 and CD40 regulates inflammation-mediated angiogenesis.
- This pathway represents a critical mechanism in the pathogenesis of vascular diseases.
- Targeting this microRNA-CD40 axis could offer new therapeutic strategies for vascular inflammation and angiogenesis-related disorders.
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