MiR181-5p promotes pathogenic angiogenesis of hepatopulmonary syndrome by negatively regulating Wnt inhibitor Wif1

作者全名："Li, Dan; Li, Guihua; Li, Caiyi; Yang, Congwen; Lu, Kaizhi"

作者地址："[Li, Dan; Lu, Kaizhi] Third Mil Med Univ, Southwest Hosp, Dept Anesthesiol, Chongqing 400038, Peoples R China; [Yang, Congwen] Chongqing Med Univ, Coll Tradit Chinese Med, Chongqing 400016, Peoples R China"

通信作者："Lu, KZ (通讯作者)，Third Mil Med Univ, Southwest Hosp, Dept Anesthesiol, Chongqing 400038, Peoples R China.; Yang, CW (通讯作者)，Chongqing Med Univ, Coll Tradit Chinese Med, Chongqing 400016, Peoples R China."

来源：IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001094009200011

JCR分区：Q3

影响因子：2.1

年份：2023

卷号：26

期号：12

开始页：1460

结束页：1467

文献类型：Article

关键词：Angiogenesis; syndrome; MiR181-5p; endothelial cells; Wnt inhibitory factor

摘要："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 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. 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."

基金机构："National Natural Science Foundation of China [81800060]; Natural Science Foundation of Chongqing, China [cstc2020jcyj-msxmX0361]; Science and Technology Project Affiliated to the Education Department of Chongqing Municipality [KJZD-K202215104]; Xinglin program of Chongqing TCM/TCM-integrated Key discipline [2021-ZDXK-yc05]"

基金资助正文："This project was supported by the National Natural Science Foundation of China [81800060) , Natural Science Foundation of Chongqing, China [cstc2020jcyj-msxmX0361] , The Science and Technology Project Affiliated to the Education Department of Chongqing Municipality [KJZD-K202215104] and Xinglin program of Chongqing TCM/TCM-integrated Key discipline [2021-ZDXK-yc05] ."