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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 
 International Journal of Molecular Sciences, Vol.19(11) : E3428, 2018 
Journal Title
 International Journal of Molecular Sciences 
Issue Date
ICAM1 ; NF-κB ; Rho GTPase ; TNF-α ; VCAM1 ; YAP/TAZ ; endothelial cells
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.
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1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Yonsei Integrative Research Institute for Cerebral & Cardiovascular Disease (뇌심혈관질환융합연구사업단) > 1. Journal Papers
Yonsei Authors
김병모(Kim, Byeong Mo) ORCID logo https://orcid.org/0000-0002-0582-3132
서미란(Seo, Mi Ran)
최현정(Choi, Hyun-Jung) ORCID logo https://orcid.org/0000-0003-3695-3420
허지회(Heo, Ji Hoe) ORCID logo https://orcid.org/0000-0001-9898-3321
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