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TNF-?-Induced YAP/TAZ Activity Mediates Leukocyte-Endothelial Adhesion by Regulating VCAM1 Expression in Endothelial Cells.

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-?. YAP/TAZ was dephosphorylated, translocated from the cytosol to the nucleus, and activated by TNF-? in endothelial cells. A specific inhibitor of Rho GTPases suppressed the TNF-?-induced dephosphorylation of YAP. Knockdown of YAP/TAZ using siRNA significantly reduced the expression of the leukocyte adhesion molecule VCAM1 induced by TNF-?. The adhesion of monocytes to endothelial cells was also markedly reduced by YAP/TAZ silencing. However, knockdown of YAP/TAZ did not affect TNF-?-induced NF-?B signaling. Overall, these results suggest that YAP/TAZ plays critical roles in regulating TNF-?-induced endothelial cell adhesive properties without affecting the NF-?B pathway, and implicate YAP/TAZ as a potential therapeutic target for treating inflammatory vascular diseases.

SUBMITTER: Choi HJ

PROVIDER: S-EPMC6274800 | biostudies-other | 2018 Nov

REPOSITORIES: biostudies-other

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TNF-α-Induced YAP/TAZ Activity Mediates Leukocyte-Endothelial Adhesion by Regulating VCAM1 Expression in Endothelial Cells.

Choi Hyun-Jung HJ Kim Na-Eun NE Kim Byeong Mo BM Seo Miran M Heo Ji Hoe JH

International journal of molecular sciences 20181101 11

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 a ...[more]

PMID: 30388809

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Dataset Information

TNF-?-Induced YAP/TAZ Activity Mediates Leukocyte-Endothelial Adhesion by Regulating VCAM1 Expression in Endothelial Cells.

Publications

TNF-α-Induced YAP/TAZ Activity Mediates Leukocyte-Endothelial Adhesion by Regulating VCAM1 Expression in Endothelial Cells.

Similar Datasets

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