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Role of MicroRNA-103a Targeting ADAM10 in Abdominal Aortic Aneurysm
Tong Jiao1, Ye Yao1, Bo Zhang1
1Department of Vascular Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
Abstract:
MicroRNAs (miRNAs) are deregulated in various vascular ailments including abdominal aortic aneurysm (AAA). MiR-103 is involved in vascular, metabolic, and malignant diseases, but whether it participates in the pathogenesis of AAA remains elusive. ADAM10 plays a vital role in the formation of aneurysm, but whether miRs modulate its activity during AAA formation is totally unknown. In this study, we detected the significantly increased protein expression of ADAM10 in angiotensin II induced murine AAA specimens, while the mRNA expression of ADAM10 was similar between AAA and control, suggesting the posttranscriptional regulation. The ADAM10 specific inhibitor GI254023X dramatically reduced the macrophage infiltration of murine abdominal aorta. Bioinformatic predictions suggest that ADAM10 is the target of miR-103a/107 but the binding site is exclusive. At the cellular level, miR-103a-1 suppressed the protein expression of ADAM10, while antisense miR-103a-1 increased its expression. Particularly, with the progression of murine AAA, the mRNA expression of miR-103a/107 substantially decreased and the protein expression of ADAM10 greatly increased. Together, our data afford the new insight that miR-103a inhibited AAA growth via targeting ADAM10, which might be a promising therapeutic strategy to alleviate AAA.
Insights
MicroRNA-103 (miR-103) inhibits abdominal aortic aneurysm (AAA) growth by targeting ADAM10. This discovery offers a potential new therapeutic strategy for treating AAA disease.
Area of Science:
- Vascular Biology
- Molecular Medicine
- Genetics
Background:
- MicroRNAs (miRNAs) are implicated in vascular diseases like abdominal aortic aneurysm (AAA).
- The role of miR-103 in AAA pathogenesis and its interaction with ADAM10, a key aneurysm factor, is unknown.
- ADAM10 protein expression increases in AAA, suggesting posttranscriptional regulation.
Purpose of the Study:
- To investigate the role of miR-103 in the pathogenesis of abdominal aortic aneurysm (AAA).
- To determine if microRNAs modulate ADAM10 activity during AAA formation.
- To explore the therapeutic potential of targeting the miR-103/ADAM10 axis in AAA.
Main Methods:
- Analysis of ADAM10 protein and mRNA expression in angiotensin II-induced murine AAA models.
- Assessment of macrophage infiltration using an ADAM10 inhibitor (GI254023X).
- Bioinformatic prediction of miR-103a/107 targeting of ADAM10.
- In vitro experiments using miR-103a mimics and inhibitors to assess effects on ADAM10 protein levels.
Main Results:
- ADAM10 protein expression was significantly elevated in AAA tissues, while mRNA levels remained unchanged, indicating posttranscriptional control.
- Inhibition of ADAM10 reduced macrophage infiltration in murine abdominal aortas.
- miR-103a suppressed ADAM10 protein expression, whereas its inhibition led to increased ADAM10 levels.
- AAA progression correlated with decreased miR-103a/107 mRNA and increased ADAM10 protein expression.
Conclusions:
- miR-103a plays an inhibitory role in abdominal aortic aneurysm (AAA) development by targeting ADAM10.
- The miR-103a/ADAM10 pathway represents a potential therapeutic target for mitigating AAA progression.
- These findings provide novel insights into the molecular mechanisms underlying AAA pathogenesis.
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