The role of 14-3-3 in the progression of vascular inflammation induced by lipopolysaccharide

  • Int Immunopharmacol. 2023 Jun:119:110220. doi: 10.1016/j.intimp.2023.110220.
Hongwei Tan  1 ,  Jinping Li  1 ,  Chunsen Jia  1 ,  Haozhong Huang  1 ,  Lei Li  1 ,  Bin Liao  2 ,  Yang Long  3 ,  Yongmei Nie  4 ,  Fengxu Yu  5
Affiliations
  • 1. Department of Cardiovascular Surgery, The Affiliated Hospital of Southwest Medical University, China.
  • 2. Department of Cardiovascular Surgery, The Affiliated Hospital of Southwest Medical University, China; Metabolic Vascular Disease Key Laboratory of Sichuan Province, China; Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, China.
  • 3. Metabolic Vascular Disease Key Laboratory of Sichuan Province, China; Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, China; Sichuan Clinical Research Center for Nephropathy, Luzhou, China.
  • 4. Department of Cardiovascular Surgery, The Affiliated Hospital of Southwest Medical University, China; Metabolic Vascular Disease Key Laboratory of Sichuan Province, China; Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, China. Electronic address: [email protected].
  • 5. Department of Cardiovascular Surgery, The Affiliated Hospital of Southwest Medical University, China; Metabolic Vascular Disease Key Laboratory of Sichuan Province, China; Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, China. Electronic address: [email protected].
PMID: 37104914 DOI: 10.1016/j.intimp.2023.110220
Abstract

Objective: To explore the role of 14-3-3 protein and the Hippo and yes-associated protein 1 (YAP) signaling pathway in lipopolysaccharide (LPS)-induced vascular inflammation.

Methods: Human umbilical vein endothelial cells (HUVECs) and C57B6 mice were treated with LPS to establish cell and animal models of vascular inflammation. Lentiviral transfection, Western blot, qPCR, immunofluorescence, immunohistochemistry, co-immunoprecipitation, and enzyme-linked immunosorbent assays were used to measure inflammatory factors and expression of 14-3-3 protein and phosphorylation of YAP at S127. HUVECs and C57B6 mice were pretreated with a YAP Inhibitor, Verteporfin, to observe changes in YAP expression and downstream vascular inflammation.

Results: LPS induced acute and chronic inflammatory responses in HUVECs and mice and upregulated the expression of several inflammatory factors. LPS also induced expression of 14-3-3 protein and phosphorylation of YAP at S127 in response to acute vascular inflammation and downregulated these markers in response to chronic vascular inflammation. Verteporfin reduced these LPS-induced effects on vascular inflammation.

Conclusion: In chronic vascular inflammation, 14-3-3 protein is downregulated, which promotes inflammation by increasing Hippo/YAP nuclear translocation.

Keywords
14-3-3 protein; Hippo pathway; Inflammation; Vascular disease; YAP.
Products