Krüppel-like factor 6 mediates pulmonary angiogenesis in rat experimental hepatopulmonary syndrome and is aggravated by bone morphogenetic protein 9

Biology Open

Yihui Yang¹  Bin Yi¹  Yunfei Zhang¹  Kaizhi Lu¹  Congwen Yang¹  Hongfu Yu¹  Xiangfa Ai¹  Xiaobo Wang² 

[1] Department of Anaesthesia, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038 China;Department of LBCMCP, Centre de Biologie Intégrative (CBI), Université de Toulouse, CNRS, UPS, 31062 Toulouse, France;

关键词: KLF6;    Hepatopulmonary syndrome (HPS);    BMP9;    Angiogenesis;   

DOI  :  10.1242/bio.040121

来源: DOAJ

【 摘 要 】

Hepatopulmonary syndrome (HPS) is a serious pulmonary vascular disease derived from chronic liver disease, and its key pathogenesis is angiogenesis. Krüppel-like factor 6 (KLF6) mediates physiological repair and remodeling during vascular injury. However, the role of KLF6 in pulmonary microvascular endothelial cells (PMVECs) during angiogenesis of HPS and its underlying mechanism in HPS have not been investigated. Common bile duct ligation (CBDL) in rats can replicate pulmonary vascular abnormalities of human HPS. Here, we found that advanced pulmonary angiogenesis and pulmonary injury score coincided with the increase of KLF6 level in PMVECs of CBDL rat; KLF6 in PMVECs was also induced while cultured with CBDL rat serum in vitro. Inhibition of KLF6 dramatically suppressed PMVEC-mediated proliferation, migration and tube formation in vivo; this may be related to the downregulation of activin receptor-like kinase-1 (ALK1) and endoglin (ENG), which are transacted by KLF6. Bone morphogenetic protein 9 (BMP9) enhanced the expression of KLF6 in PMVECs and was involved in the angiogenesis of HPS. These results suggest that KLF6 triggers PMVEC-mediated angiogenesis of HPS and is aggravated by BMP9, and the inhibition of the BMP9/KLF6 axis may be an effective strategy for HPS treatment.

【 授权许可】

Unknown