Dan Li - Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, ۴۰۰۰۳۸, China
Guihua Li - Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, ۴۰۰۰۳۸, China
Caiyi Li - Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, ۴۰۰۰۳۸, China
Congwen Yang - College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, ۴۰۰۰۱۶, China
Kaizhi Lu - Department of Anesthesiology, Southwest Hospital, Third Military Medical University, Chongqing, ۴۰۰۰۳۸, China

Objective(s): Hepatopulmonary syndrome is a serious respiratory injury caused by chronic liver disease. Excessive pulmonary capillary angiogenesis is the key pathological event. However, the mechanism of microRNA regulatory pulmonary capillary angiogenesis is still unclear.Materials and Methods: The hepatopulmonary syndrome rat model was constructed by Common bile duct ligation (CBDL) surgery. The expression tread of miR۱۸۱-۵p and Wif۱ was detected by qRT-PCR and western blot in various tissues and disease processes. Wif۱ was predicted as one of the potential target genes of miR۱۸۱-۵p by bioinformatic assay. miR۱۸۱-۵p mimics and inhibitors were used to increase/decrease miR۱۸۱-۵p levels in pulmonary microvascular cells. And Wif-۱ specific recombinant lentiviruses were used to up-regulate and down-regulate Wif۱ in pulmonary microvascular cells. Then, CCK۸, 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 miR۱۸۱-۵p may direct regulate Wif-۱ in HPS rats. Results: The result showed miR۱۸۱-۵p specifically activates the Wnt signaling pathway by inhibiting Wif۱ and then promotes pulmonary microvascular cell proliferation, migration, and tube formation, thereby accelerating the process of HPS. We finally verified Wif۱ as a novel and direct target of miR۱۸۱-۵p in HPS. Conclusion: Taken together, we revealed an important miR-۱۸۱-۵p/Wif۱/Wnt pathway in regulating pathological angiogenesis. It will prove beneficial as a therapeutic strategy for hepatopulmonary syndrome.

Angiogenesis, Hepatopulmonary - syndrome, MiR۱۸۱-۵p, Pulmonary microvascular - endothelial cells, Wnt inhibitory factor-۱