Role of LPA and the Hippo pathway on apoptosis in salivary gland epithelial cells.
Role of LPA and the Hippo pathway on apoptosis in salivary gland epithelial cells.
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DOI：
10.1038/emm.2014.77
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发表时间：
2014-12-12
影响因子：
12.8
通讯作者：
Park, Kyungpyo
中科院分区：
文献类型：
--
作者：
Hwang, Sung-Min;Jin, MeiHong;Shin, Yong Hwan;Choi, Seul Ki;Namkoong, Eun;Kim, MinKyoung;Park, Moon-Yong;Park, Kyungpyo
溶血磷脂酸（LPA）是一种生物活性溶血磷脂，参与多种生理反应。然而，LPA受体的表达和Hippo信号通路在上皮细胞中的作用仍然是未知的。本实验采用逆转录pcr、荧光显微法、免疫印迹法和免疫细胞化学等方法，研究了唾液腺上皮细胞中LPA受体的功能表达及其信号通路。我们发现LPA受体通过Lats/Mob1和RhoA/ROCK功能表达并参与激活由YAP/TAZ介导的Hippo通路。在lpa处理的细胞中也观察到YAP/ taz依赖的靶基因，包括CTGF、ANKRD1和CYR61的上调。此外，基于肿瘤坏死因子(TNF)-α诱导细胞凋亡的数据，LPA上调TNF诱导的caspase-3和cleaved Poly（adp -核糖）聚合酶（PARP）。然而，小干扰RNA处理yes相关蛋白（YAP）或带pdz结合基序的转录共激活因子（TAZ）可显著降低TNF-α-和lpa诱导的细胞凋亡，表明YAP和TAZ调节了唾液上皮细胞的凋亡途径。
Lysophosphatidic acid (LPA) is a bioactive lysophospholipid involved in numerous physiological responses. However, the expression of LPA receptors and the role of the Hippo signaling pathway in epithelial cells have remained elusive. In this experiment, we studied the functional expression of LPA receptors and the associated signaling pathway using reverse transcriptase–PCR, microspectrofluorimetry, western blotting and immunocytochemistry in salivary gland epithelial cells. We found that LPA receptors are functionally expressed and involved in activating the Hippo pathway mediated by YAP/TAZ through Lats/Mob1 and RhoA/ROCK. Upregulation of YAP/TAZ-dependent target genes, including CTGF, ANKRD1 and CYR61, has also been observed in LPA-treated cells. In addition, based on data suggesting that tumor necrosis factor (TNF)-α induces cell apoptosis, LPA upregulates TNF-induced caspase-3 and cleaved Poly(ADP-ribose)polymerase (PARP). However, small interfering RNA treatment to Yes-associated protein (YAP) or transcriptional co-activator with a PDZ-binding motif (TAZ) significantly decreased TNF-α- and LPA-induced apoptosis, suggesting that YAP and TAZ modulate the apoptotic pathway in salivary epithelial cells.
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影响因子：
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作者：
Jeong, Geun Ok;Shin, Sang Hun;Kim, Jae Ho
通讯作者：
Kim, Jae Ho
影响因子：
3.7
作者：
Juric V;Chen CC;Lau LF
通讯作者：
Lau LF
影响因子：
5.3
作者：
Almodovar-Garcia, Karinna;Kwon, Minjae;Davidson, Jeffrey M.
通讯作者：
Davidson, Jeffrey M.
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：
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影响因子：
64.5
作者：
Yu FX;Zhao B;Panupinthu N;Jewell JL;Lian I;Wang LH;Zhao J;Yuan H;Tumaneng K;Li H;Fu XD;Mills GB;Guan KL
通讯作者：
Guan KL