Tnf-α-induced yap/taz activity mediates leukocyte-endothelial adhesion by regulating vcam1 expression in endothelial cells

Hyun Jung Choi, Na Eun Kim, Byeong Mo Kim, Miran Seo, Ji Hoe Heo

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

YAP/TAZ, a transcriptional co-activator of Hippo pathway, has emerged as a central player in vessel homeostasis such as sprouting angiogenesis and vascular barrier stabilization, during development. However, the role of YAP/TAZ in pathological angiogenesis remains unclear. Here, we demonstrated that YAP/TAZ is a critical mediator in leukocyte-endothelial adhesion induced by the vascular inflammatory cytokine TNF-α. YAP/TAZ was dephosphorylated, translocated from the cytosol to the nucleus, and activated by TNF-α in endothelial cells. A specific inhibitor of Rho GTPases suppressed the TNF-α-induced dephosphorylation of YAP. Knockdown of YAP/TAZ using siRNA significantly reduced the expression of the leukocyte adhesion molecule VCAM1 induced by TNF-α. The adhesion of monocytes to endothelial cells was also markedly reduced by YAP/TAZ silencing. However, knockdown of YAP/TAZ did not affect TNF-α-induced NF-κB signaling. Overall, these results suggest that YAP/TAZ plays critical roles in regulating TNF-α-induced endothelial cell adhesive properties without affecting the NF-κB pathway, and implicate YAP/TAZ as a potential therapeutic target for treating inflammatory vascular diseases.

Original languageEnglish
Article number3428
JournalInternational journal of molecular sciences
Volume19
Issue number11
DOIs
Publication statusPublished - 2018 Nov 1

Bibliographical note

Funding Information:
Funding: This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2015R1D1A1A01056703) and by a grant of the Korea Healthcare Technology R&D Project, Ministry for Health & Welfare Affairs (HI08C2149), Republic of Korea. This study was also supported by a faculty research grant of Yonsei University College of Medicine in 2016 (2016-32-0063; 2017-32-0101).

Publisher Copyright:
© 2018 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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