Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Endothelial cell–glucocorticoid receptor interactions and regulation of Wnt signaling
Han Zhou, … , William C. Sessa, Julie E. Goodwin
Han Zhou, … , William C. Sessa, Julie E. Goodwin
Published February 13, 2020
Citation Information: JCI Insight. 2020;5(3):e131384. https://doi.org/10.1172/jci.insight.131384.
View: Text | PDF
Research Article Inflammation Vascular biology

Endothelial cell–glucocorticoid receptor interactions and regulation of Wnt signaling

  • Text
  • PDF
Abstract

Vascular inflammation is present in many cardiovascular diseases, and exogenous glucocorticoids have traditionally been used as a therapy to suppress inflammation. However, recent data have shown that endogenous glucocorticoids, acting through the endothelial glucocorticoid receptor, act as negative regulators of inflammation. Here, we performed ChIP for the glucocorticoid receptor, followed by next-generation sequencing in mouse endothelial cells to investigate how the endothelial glucocorticoid receptor regulates vascular inflammation. We identified a role of the Wnt signaling pathway in this setting and show that loss of the endothelial glucocorticoid receptor results in upregulation of Wnt signaling both in vitro and in vivo using our validated mouse model. Furthermore, we demonstrate glucocorticoid receptor regulation of a key gene in the Wnt pathway, Frzb, via a glucocorticoid response element gleaned from our genomic data. These results suggest a role for endothelial Wnt signaling modulation in states of vascular inflammation.

Authors

Han Zhou, Sameet Mehta, Swayam Prakash Srivastava, Kariona Grabinska, Xinbo Zhang, Chris Wong, Ahmad Hedayat, Paola Perrotta, Carlos Fernández-Hernando, William C. Sessa, Julie E. Goodwin

×

Figure 6

In vivo regulation of canonical Wnt signaling.

Options: View larger image (or click on image) Download as PowerPoint
In vivo regulation of canonical Wnt signaling.
(A) Representative aortas...
(A) Representative aortas stained with Oil Red O from Apoe–/– and double KO (DKO) mice. Scale bar: 1 cm. (B) Quantification of lesion size in each genotype (n = 5/group). (C) Representative aortas stained with X-gal demonstrate significantly higher β-galactosidase staining in DKO mice. A LacZ(–) control is included for comparison. Scale bar: 1 cm. (D) Quantification of β-gal expression in each genotype (n = 3–7 mice/group). (E) mRNA expression of Axin 2, ctnnb, and TCF/LEF is significantly higher in aortic endothelial cells from DKO mice than Apoe–/– mice after diet feeding (n = 5/group). Student’s t test was used to analyze data. **P < 0.05.

Copyright © 2022 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts