Conclusion
Taken together, we revealed an important miR-181-5p/Wif1/Wnt pathway in regulating pathological angiogenesis. It will prove beneficial as a therapeutic strategy for hepatopulmonary syndrome.
Methods
The hepatopulmonary syndrome rat model was constructed by Common bile duct ligation (CBDL) surgery. The expression tread of miR181-5p and Wif1 was detected by qRT-PCR and western blot in various tissues and disease processes. Wif1 was predicted as one of the potential target genes of miR181-5p by bioinformatic assay. miR181-5p mimics and inhibitors were used to increase/decrease miR181-5p levels in pulmonary microvascular cells. And Wif-1 specific recombinant lentiviruses were used to up-regulate and down-regulate Wif1 in pulmonary microvascular cells. Then, CCK8, Transwell, and tube formation assay were used for pulmonary microvascular cell proliferation, migration, and tube formation. And Dual-luciferase reporter assay was used to assess that miR181-5p may direct regulate Wif-1 in HPS rats.
Results
The result showed miR181-5p specifically activates the Wnt signaling pathway by inhibiting Wif1 and then promotes pulmonary microvascular cell proliferation, migration, and tube formation, thereby accelerating the process of HPS. We finally verified Wif1 as a novel and direct target of miR181-5p in HPS.