2. Academic Validation
  3. SCAP contributes to embryonic angiogenesis by negatively regulating KISS-1 expression in mice

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

  • Cell Death Dis. 2023 Apr 6;14(4):249. doi: 10.1038/s41419-023-05754-8.
Guo Zheng # 1,  Yu Su # 1,  Li Wei # 1,  Yingcheng Yao 1,  Yizhe Wang 1,  Xiaoting Luo 1,  Xing Wang 1,  Xiong Z Ruan 1 2,  Danyang Li 3,  Yaxi Chen 4
Affiliations

Affiliations

  • 1 Centre for Lipid Research & Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, China.
  • 2 John Moorhead Research Laboratory, Centre for Nephrology, University College London Medical School, Royal Free Campus, University College London, London, NW3 2PF, UK.
  • 3 Centre for Lipid Research & Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, China. lidycq@cqmu.edu.cn.
  • 4 Centre for Lipid Research & Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, China. chenyaxi@cqmu.edu.cn.
  • # Contributed equally.
PMID: 37024487 DOI: 10.1038/s41419-023-05754-8
Abstract

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.

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