The YAP signaling pathway promotes the progression of lymphatic malformations through the activation of lymphatic endothelial cells
The YAP signaling pathway promotes the progression of lymphatic malformations through the activation of lymphatic endothelial cells
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YAP信号通路通过激活淋巴管内皮细胞促进淋巴管畸形的进展
DOI：
10.1038/s41390-020-0863-0
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发表时间：
2020-04
影响因子：
3.6
通讯作者：
Yu Cai
中科院分区：
文献类型：
--
作者：
Wenqun Zhong;Hao Jiang;Yanping Zou;Jiangang Ren;Zhizheng Li;Kefei He;Jihong Zhao;Xiaoshun Zhou;Dongsheng Mou;Yu Cai
为探讨雅普/TAZ（Yes-associated protein/transformational coactivator with PDZ binding motif）通路在淋巴管畸形（LM）发病中的作用，采用免疫组织化学方法检测雅普、TAZ、CTGF和Ki-67在LM中的表达。免疫荧光双标法分析雅普和Ki-67的共定位。通过Pearson相关分析和聚类分析，分析这些蛋白质之间的关系。人真皮淋巴管内皮细胞（HDLECs）用于机制研究。结果与正常皮肤相比，淋巴管内皮细胞（LECs）中雅普、TAZ、CTGF和Ki-67的表达水平均显著上调。有趣的是，雅普和CTGF在感染的LM中呈现高得多的表达水平。在体外实验中，脂多糖（LPS）通过增加Erk 1/2（细胞外信号调节激酶1/2）的磷酸化，以浓度和时间依赖性的方式增强雅普的表达。此外，HDLECs的增殖、侵袭和小管形成与雅普信号通路的激活相一致。此外，LM大鼠模型验证了LPS促进LM的发生，而这种促进作用依赖于雅普的激活。结论数据表明，LECs中雅普信号通路的激活可能在LM的发生中发挥关键作用。影响与正常皮肤相比，LM的LECs中雅普信号通路被激活。抑制雅普信号通路可减弱HDLEC的增殖、侵袭和小管形成。另外，雅普信号通路的激活可促进大鼠LM的发生发展，雅普信号通路在LECs中的激活可能在LM的发生发展中起重要作用，雅普信号通路在LM中被激活。抑制雅普信号通路可促进病变消退。
BackgroundTo investigate whether the YAP/TAZ (Yes-associated protein/transcriptional coactivator with PDZ binding motif) pathway contributes to the pathogenesis of lymphatic malformations (LMs).MethodsYAP, TAZ, CTGF (connective tissue growth factor), and Ki-67 were detected in LMs by immunohistochemistry. The colocalization of YAP and Ki-67 was analyzed by double immunofluorescence. Pearson’s correlation and cluster analyses were performed to analyze the relationships between these proteins. Human dermal lymphatic endothelial cells (HDLECs) were used for mechanistic investigation. Rat models of LMs were established to investigate the role of the YAP pathway in LM development.ResultsCompared with those in normal skin, the expression levels of YAP, TAZ, CTGF, and Ki-67 were significantly upregulated in lymphatic endothelial cells (LECs) of LMs. Interestingly, YAP and CTGF presented much higher expression levels in infected LMs. In experiments in vitro, lipopolysaccharide (LPS) enhanced the expression of YAP in a concentration- and time-dependent manner via the increased phosphorylation of Erk1/2 (extracellular signal-regulated kinase 1/2). Moreover, the proliferation, invasion, and tubule formation of HDLECs increased significantly in accordance with the activation of the YAP signaling pathway. Furthermore, LM rat models validated that LPS facilitated the development of LMs, which was dependent on the activation of YAP.ConclusionsThe data reveal that activation of the YAP signaling pathway in LECs may play a crucial role in the progression of LMs.ImpactCompared with that in normal skin, the YAP signaling pathway was activated in LECs of LMs. Inhibiting the YAP signaling pathway attenuated the proliferation, invasion, and tubule formation of HDLECs. Additionally, the activation of the YAP signaling pathway could promote LM development in a rat model.Activation of the YAP signaling pathway in LECs may play a crucial role in the progression of LMs.The YAP signaling pathway was activated in LMs. Inhibition of the YAP signaling pathway could promote regression of the lesions.
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DOI：
10.1055/b-0034-77914
发表时间：
2018-10
期刊：
Greenfield's Neuropathology - Two Volume Set
影响因子：
--
作者：
Huy M Do
通讯作者：
Huy M Do
MEK1 促进 YAP 且它们的相互作用对于肝癌的肿瘤发生至关重要
影响因子：
3.5
作者：
Li, Lanlan;Wang, Jiayi;Sun, Fenyong
通讯作者：
Sun, Fenyong
Hippo 通路在器官大小控制、组织稳态和癌症中的作用
影响因子：
64.5
作者：
Yu FX;Zhao B;Guan KL
通讯作者：
Guan KL
DOI：
10.1016/j.ajpath.2017.07.019
发表时间：
2017-11
期刊：
The American journal of pathology
影响因子：
--
作者：
Jie-gang Yang;Yan-fang Sun;Ke-fei He;Jian-Gang Ren;Zhuo-Jue Liu;Bing Liu;W. Zhang;Yi-Fang Zhao
通讯作者：
Jie-gang Yang;Yan-fang Sun;Ke-fei He;Jian-Gang Ren;Zhuo-Jue Liu;Bing Liu;W. Zhang;Yi-Fang Zhao
影响因子：
0.9
作者：
Hassanein, Aladdin H.;Mulliken, John B.;Greene, Arin K.
通讯作者：
Greene, Arin K.