SCAP contributes to embryonic angiogenesis by negatively regulating KISS-1 expression in mice

作者全名："Zheng, Guo; Su, Yu; Wei, Li; Yao, Yingcheng; Wang, Yizhe; Luo, Xiaoting; Wang, Xing; Ruan, Xiong Z. Z.; Li, Danyang; Chen, Yaxi"

作者地址："[Zheng, Guo; Su, Yu; Wei, Li; Yao, Yingcheng; Wang, Yizhe; Luo, Xiaoting; Wang, Xing; Ruan, Xiong Z. Z.; Li, Danyang; Chen, Yaxi] Chongqing Med Univ, Affiliated Hosp 2, Ctr Lipid Res, Chongqing 400016, Peoples R China; [Zheng, Guo; Su, Yu; Wei, Li; Yao, Yingcheng; Wang, Yizhe; Luo, Xiaoting; Wang, Xing; Ruan, Xiong Z. Z.; Li, Danyang; Chen, Yaxi] Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Dept Infect Dis,Key Lab Mol Biol Infect Dis Minist, Chongqing 400016, Peoples R China; [Ruan, Xiong Z. Z.] UCL, Univ Coll London Med Sch, Ctr Nephrol, John Moorhead Res Lab, Royal Free Campus, London NW3 2PF, England"

通信作者："Li, DY; Chen, YX (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Ctr Lipid Res, Chongqing 400016, Peoples R China.; Li, DY; Chen, YX (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Dept Infect Dis,Key Lab Mol Biol Infect Dis Minist, Chongqing 400016, Peoples R China."

来源：CELL DEATH & DISEASE

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001002127600007

JCR分区：Q1

影响因子：8.1

年份：2023

卷号：14

期号：4

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) is indispensable in organ development because it maintains intracellular cholesterol homeostasis. The vessel is not widely conceived of as a cholesterol-sensitive tissue, so the specific role of SCAP in angiogenesis has not been paid attention to. As an important component of the vascular mesoderm, vascular smooth muscle cells (VSMCs) are widely involved in each step of angiogenesis. Here, we report for the first time that VSMC-specific ablation of SCAP inhibits VSMC proliferation and migration, interacting with endothelial cells (ECs), and finally causes defective embryonic angiogenesis in mice. Mechanistically, we demonstrated that SCAP ablation in VSMCs leads to the upregulation of KISS-1 protein, consequently resulting in suppressed activation of the MAPK/ERK signaling pathway and downregulation of matrix metalloproteinase 9 (MMP9) and vascular endothelial-derived growth factor (VEGF) expression to prevent angiogenesis. Importantly, we found that SCAP promotes the cleavage and nuclear translocation of SREBP2, which acts as a negative transcription regulator, regulating KISS-1 expression. Our findings suggest that SCAP contributes to embryonic angiogenesis by negatively regulating KISS-1 expression in mice and provide a new point of view for therapeutic targets of vascular development."

基金机构："National Natural Science Foundation of China [82170586, 81900406]; Chongqing Research Program of Basic Research and Frontier Technology [cstc2020jcyj-zdxmX0007]; Science and Technology Research Program of Chongqing Municipal Education Commission [KJZD-K202200402]; Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University; 111 Project [D20028]; CQMU Program for Youth Innovation in Future Medicine"

基金资助正文："This work was supported by the National Natural Science Foundation of China (No.82170586, 81900406); the Chongqing Research Program of Basic Research and Frontier Technology (cstc2020jcyj-zdxmX0007); the Science and Technology Research Program of Chongqing Municipal Education Commission (Grant No. KJZD-K202200402); Kuanren Talents Program of the second affiliated hospital of Chongqing Medical University; the 111 Project (No. D20028). CQMU Program for Youth Innovation in Future Medicine."