MiR26-5p inhibits pathological pulmonary microvascular angiogenesis via down-regulating WNT5A

Document Type : Original Article

Authors

1 Department of Anesthesiology, People’s Hospital of Chongqing Banan District, Chongqing 401320, China

2 Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical and Pharmaceutical College, Chongqing 400038, China

3 Southwest Hospital, Third Military Medical University, Chongqing 400038, China

4 Department of Anesthesiology, The Ninth People’s Hospital of Chongqing, Chongqing 400700, China

Abstract

Objective(s): 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.

Keywords

Main Subjects

References

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Iranian Journal of Basic Medical Sciences
Volume 26, Issue 7
July 2023
Pages 812-819

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