YAP determines the cell fate of injured mouse hepatocytes in vivo.
YAP determines the cell fate of injured mouse hepatocytes in vivo.
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DOI：
10.1038/ncomms16017
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发表时间：
2017-07-06
影响因子：
16.6
通讯作者：
Nishina H
中科院分区：
文献类型：
--
作者：
Miyamura N;Hata S;Itoh T;Tanaka M;Nishio M;Itoh M;Ogawa Y;Terai S;Sakaida I;Suzuki A;Miyajima A;Nishina H
衰老、转化或受损细胞的存在会损害组织功能或导致肿瘤发生;因此，生物体已经进化出质量控制机制来消除它们。在这里，我们表明，雅普激活诱导的失活的海马途径，特别是在受损的肝细胞促进其选择性消除，通过使用在小鼠肝脏中的体内镶嵌分析。这些受损的肝细胞迁移到肝窦，经历凋亡并被枯否细胞吞噬。相反，未受损肝细胞中的雅普活化导致增殖。在活化的雅普的存在下，细胞应激（如乙醇）损伤肝窦内皮细胞和肝细胞，将细胞命运从增殖转变为迁移/凋亡。这涉及调节细胞迁移的CDC 42和Rac的激活。因此，我们认为，雅普作为一个应力传感器，诱导消除受损细胞，以维持组织和器官的稳态。衰老和受损的细胞影响组织功能，并可能导致肿瘤发生。因此，有效消除这些细胞对于组织完整性至关重要。Miyamura等人在此表明，雅普可作为细胞应激传感器，促进受损细胞的清除，以维持组织稳态。
The presence of senescent, transformed or damaged cells can impair tissue function or lead to tumorigenesis; therefore, organisms have evolved quality control mechanisms to eliminate them. Here, we show that YAP activation induced by inactivation of the Hippo pathway specifically in damaged hepatocytes promotes their selective elimination by using in vivo mosaic analysis in mouse liver. These damaged hepatocytes migrate into the hepatic sinusoids, undergo apoptosis and are engulfed by Kupffer cells. In contrast, YAP activation in undamaged hepatocytes leads to proliferation. Cellular stresses such as ethanol that damage both liver sinusoidal endothelial cells and hepatocytes switch cell fate from proliferation to migration/apoptosis in the presence of activated YAP. This involves the activation of CDC42 and Rac that regulate cell migration. Thus, we suggest that YAP acts as a stress sensor that induces elimination of injured cells to maintain tissue and organ homeostasis. Senescent and injured cells affect tissue functions and can drive tumorigenesis. Thus, efficient elimination of these cells is pivotal for tissue integrity. Here Miyamura et al. show that YAP acts as a cellular stress sensor and promotes the elimination of damaged cells to maintain tissue homeostasis.
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影响因子：
64.8
作者：
Kang, Tae-Won;Yevsa, Tetyana;Zender, Lars
通讯作者：
Zender, Lars
影响因子：
3.5
作者：
Budker, Vladimir G.;Subbotin, Vladimir M.;Wolff, Jon A.
通讯作者：
Wolff, Jon A.
影响因子：
3.8
作者：
Hamdy, Nadia;El-Demerdash, Ebtehal
通讯作者：
El-Demerdash, Ebtehal
DOI：
10.1038/nrd4161
发表时间：
2014-01
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
通讯作者：
--
肝冠状结构：小鼠和人类非酒精性脂肪性肝炎的独特组织学特征。
影响因子：
3.7
作者：
Itoh M;Kato H;Suganami T;Konuma K;Marumoto Y;Terai S;Sakugawa H;Kanai S;Hamaguchi M;Fukaishi T;Aoe S;Akiyoshi K;Komohara Y;Takeya M;Sakaida I;Ogawa Y
通讯作者：
Ogawa Y