TNF-α-Induced YAP/TAZ Activity Mediates Leukocyte-Endothelial Adhesion by Regulating VCAM1 Expression in Endothelial Cells.
TNF-α-Induced YAP/TAZ Activity Mediates Leukocyte-Endothelial Adhesion by Regulating VCAM1 Expression in Endothelial Cells.
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DOI：
10.3390/ijms19113428
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发表时间：
2018-11-01
影响因子：
5.6
通讯作者：
Heo JH
中科院分区：
文献类型：
--
作者：
Choi HJ;Kim NE;Kim BM;Seo M;Heo JH
雅普/TAZ是Hippo通路的转录共激活因子，在发育过程中参与了血管的生长和血管屏障的稳定。然而，雅普/TAZ在病理性血管生成中的作用仍不清楚。在这里，我们证明了雅普/TAZ是血管炎性细胞因子TNF-α诱导的白细胞-内皮细胞粘附的关键介质。在内皮细胞中，雅普/TAZ被TNF-α激活，并发生去磷酸化。Rho GTPases特异性抑制剂可抑制TNF-α诱导的雅普去磷酸化。用siRNA敲低雅普/TAZ可显著降低TNF-α诱导的白细胞粘附分子VCAM 1的表达。雅普/TAZ沉默也显著降低单核细胞与内皮细胞的粘附。然而，敲低雅普/TAZ并不影响TNF-α诱导的NF-κB信号转导。总之，这些结果表明雅普/TAZ在调节TNF-α诱导的内皮细胞粘附特性中起关键作用，而不影响NF-κB通路，并暗示雅普/TAZ作为治疗炎性血管疾病的潜在治疗靶点。
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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影响因子：
64.8
作者：
Taniguchi, Koji;Wu, Li-Wha;Grivennikov, Sergei I.;de Jong, Petrus R.;Lian, Ian;Yu, Fa-Xing;Wang, Kepeng;Ho, Samuel B.;Boland, Brigid S.;Chang, John T.;Sandborn, William J.;Hardiman, Gary;Raz, Eyal;Maehara, Yoshihiko;Yoshimura, Akihiko;Zucman-Rossi, Jessica;Guan, Kun-Liang;Karin, Michael
通讯作者：
Karin, Michael
影响因子：
20.1
作者：
Lv Y;Kim K;Sheng Y;Cho J;Qian Z;Zhao YY;Hu G;Pan D;Malik AB;Hu G
通讯作者：
Hu G
影响因子：
15.9
作者：
MARUI, N;OFFERMANN, MK;MEDFORD, RM
通讯作者：
MEDFORD, RM
影响因子：
4
作者：
Gumbiner, Barry M.;Kim, Nam-Gyun
通讯作者：
Kim, Nam-Gyun
影响因子：
3.8
作者：
Choi HJ;Kwon YG
通讯作者：
Kwon YG