2. Academic Validation
  3. Cyclophilin A-FoxO1 signaling pathway in endothelial cell apoptosis

Cyclophilin A-FoxO1 signaling pathway in endothelial cell apoptosis

  • Cell Signal. 2019 Sep;61:57-65. doi: 10.1016/j.cellsig.2019.04.014.
Yifan Xie 1,  Xiaotao Li 2,  Junbo Ge 3
Affiliations

Affiliations

  • 1 Institute of Biomedical Science, Fudan University, Shanghai 200032, China; Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China.
  • 2 Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University, Shanghai 200241, China; Department of Molecular and Cellular Biology, The Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA. Electronic address: xiaotaol@bcm.edu.
  • 3 Institute of Biomedical Science, Fudan University, Shanghai 200032, China; Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China. Electronic address: jbge@zs-hospital.sh.cn.
PMID: 31063815 DOI: 10.1016/j.cellsig.2019.04.014
Abstract

Cyclophilin A (CyPA), which is encoded by PPIA, is a ubiquitously expressed intracellular protein and is secreted in response to inflammatory stimuli. CyPA stimulates proinflammatory signaling pathways in vascular smooth muscle cells (VSMCs) and endothelial cells (ECs), promotes VSMC migration and proliferation, EC adhesion molecules expression, and inflammatory cell chemotaxis and Apoptosis. Moreover, CyPA activates mitogen-activated protein kinases, including ERK1/2, JNK, and p38, and stimulates IkB-α phosphorylation, NF-kB activation, and vascular cell adhesion molecule-1 and E-Selectin expression in human umbilical vein ECs. Therefore, we hypothesized that CyPA regulated transcription factor FoxO1 phosphorylation and transcriptional activity and the expression of downstream genes involved in vascular EC activation, thus activated vascular ECs in vitro. We found that intracellular CyPA promoted FoxO1 dephosphorylation at Ser256, nuclear accumulation, and transcriptional activity by interacting with it. Moreover, CyPA induced FoxO1-dependent expression of downstream genes involved in EC chemotaxis and Apoptosis, including monocyte chemoattractant protein-1 and BCL-2-interacting mediator of cell death, and stimulated the Apoptosis of human umbilical vein ECs in vitro.

Keywords

Chemotaxis and apoptosis molecules; Cyclophilin A; Endothelial cell apoptosis; FoxO1.

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