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Updated: Jul 24, 2025
Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
MiR26-5p inhibits pathological pulmonary microvascular angiogenesis via down-regulating WNT5A
Jie Chen1,2, Feng Gao3,2, Dan Li4
1Department of Anesthesiology, People's Hospital of Chongqing Banan District, Chongqing 401320, China.
Objectives:
Pathological micro angiogenesis is a key pathogenic factor in pulmonary diseases such as pulmonary hypertension and hepatopulmonary syndrome. More and more pieces of evidence show that excessive proliferation of pulmonary microvascular endothelial cells is the key event of pathological micro angiogenesis. The purpose of this research is to reveal the mechanism of miR26-5p regulating pulmonary microvascular hyperproliferation.
Materials And Methods:
Hepatopulmonary syndrome rat model was made by common bile duct ligation. HE and IHC staining were used for analysis of the pathology of the rat. CCK8, transwell, and wound healing assay were used to assess miR26-5p or target gene WNT5A functioned toward PMVECs. microRNA specific mimics and inhibitors were used for up/down-regulated miR26-5p expression in PMVECs. Recombinant lentivirus was used for overexpression/knockdown WNT5A expression in PMVECs. And the regulation relationship of miR26-5p and WNT5A was analyzed by dual-luciferase reporter assay.
Results:
qPCR showed that miR26-5p was significantly down-regulated in the course of HPS disease. Bioinformatics data showed that WNT5A was one of the potential key target genes of miR26-5p. Immunohistochemistry and qPCR analysis showed that WNT5A was largely expressed in pulmonary microvascular endothelial cells, in addition, this molecule was significantly up-regulated with the progression of the disease. Furthermore, dual luciferase reporter assay showed that miR26-5p could bind to WNT5A 3 'UTR region to inhibit WNT5A synthesis.
Conclusion:
The results suggested MiR26-5p negatively regulated PMVECs proliferation and migration by WNT5A expression. Overexpression of miR26-5p may be a potentially beneficial strategy for HPS therapy.
Insights
MicroRNA-26-5p (miR26-5p) is downregulated in hepatopulmonary syndrome (HPS) and inhibits pulmonary microvascular endothelial cell proliferation by targeting WNT5A. Upregulating miR26-5p may offer a therapeutic strategy for HPS.
Area of Science:
- Pulmonary vascular disease research
- Molecular mechanisms of angiogenesis
- MicroRNA therapeutics
Background:
- Pathological microangiogenesis, driven by excessive proliferation of pulmonary microvascular endothelial cells (PMVECs), is central to diseases like pulmonary hypertension and hepatopulmonary syndrome (HPS).
- Understanding the molecular regulation of PMVEC proliferation is crucial for developing effective therapies.
Purpose of the Study:
- To elucidate the regulatory mechanism of miR26-5p in controlling pulmonary microvascular hyperproliferation.
- To investigate the role of miR26-5p in the pathogenesis of HPS.
Main Methods:
- Hepatopulmonary syndrome rat model creation via common bile duct ligation.
- Cellular assays (CCK8, Transwell, wound healing) to evaluate miR26-5p and WNT5A function in PMVECs.
- Molecular techniques including qPCR, immunohistochemistry, dual-luciferase reporter assay, and lentivirus-mediated gene manipulation to confirm interactions.
Main Results:
- miR26-5p was significantly downregulated in HPS, while its target gene WNT5A was upregulated in PMVECs.
- miR26-5p directly binds to the 3'UTR of WNT5A, inhibiting its synthesis.
- miR26-5p negatively regulated PMVEC proliferation and migration, mediated by WNT5A expression.
Conclusions:
- miR26-5p acts as a negative regulator of PMVEC proliferation and migration through the WNT5A pathway.
- Overexpression of miR26-5p presents a potential therapeutic avenue for HPS treatment.
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