Regulation of lens gap junctions by Transforming Growth Factor beta.
Regulation of lens gap junctions by Transforming Growth Factor beta.
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DOI：
10.1091/mbc.e10-01-0055
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发表时间：
2010-05-15
影响因子：
3.3
通讯作者：
Musil LS
中科院分区：
文献类型：
--
作者：
Boswell BA;VanSlyke JK;Musil LS
使用培养的透镜上皮细胞，我们发现了FGF和TGF-β通路之间的新型串扰，以及TGF-β和p38激酶在间隙连接细胞间通讯调节中的新作用。我们的研究结果为病理性增加的TGF-β信号传导如何促进白内障形成提供了解释。间隙连接介导的细胞间通讯（GJIC）对于包括透镜在内的许多器官的正常功能至关重要。在透镜上皮细胞中的GJIC在浓度依赖性过程中被FGF增加，该过程与透镜透明度所需的GJIC的晶状体内梯度有关。与FGF不同，TGF-β水平升高与透镜功能障碍相关。我们发现，TGF-β1或-2上调染料偶联在鸡透镜上皮细胞（解离细胞衍生的单层培养物[DCDMLs]）的无血清原代培养物中通过一种不同于其他生长因子所利用的机制。值得注意的是，如果DCDMLs同时暴露于两种因子，尽管细胞-细胞接触未减少，但TGF-β和FGF上调GJIC的能力被消除。染料偶联的这种减少可归因于间隙连接组装的抑制。如果p38激酶的活性被阻断，含有连接蛋白45.6、43和56的间隙连接被恢复，并且细胞间染料偶联增加。我们的数据揭示了FGF和TGF-β通路之间的新型串扰，以及TGF-β和p38激酶在GJIC调节中的新作用。他们还解释了病理性增加的TGF-β信号传导如何有助于白内障形成。
Using cultured lens epithelial cells, we discovered a new type of cross-talk between the FGF and TGF-β pathways, as well as a novel role for TGF-β and p38 kinase in the regulation of gap junctional intercellular communication. Our findings provide an explanation for how pathologically increased TGF-β signaling could contribute to cataract formation. Gap junction–mediated intercellular communication (GJIC) is essential for the proper function of many organs, including the lens. GJIC in lens epithelial cells is increased by FGF in a concentration-dependent process that has been linked to the intralenticular gradient of GJIC required for lens transparency. Unlike FGF, elevated levels of TGF-β are associated with lens dysfunction. We show that TGF–β1 or -2 up-regulates dye coupling in serum-free primary cultures of chick lens epithelial cells (dissociated cell-derived monolayer cultures [DCDMLs]) via a mechanism distinct from that utilized by other growth factors. Remarkably, the ability of TGF-β and of FGF to up-regulate GJIC is abolished if DCDMLs are simultaneously exposed to both factors despite undiminished cell–cell contact. This reduction in dye coupling is attributable to an inhibition of gap junction assembly. Connexin 45.6, 43, and 56–containing gap junctions are restored, and intercellular dye coupling is increased, if the activity of p38 kinase is blocked. Our data reveal a new type of cross-talk between the FGF and TGF-β pathways, as well as a novel role for TGF-β and p38 kinase in the regulation of GJIC. They also provide an explanation for how pathologically increased TGF-β signaling could contribute to cataract formation.
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影响因子：
64.5
作者：
Gong, XH;Li, E;Gilula, NB
通讯作者：
Gilula, NB
影响因子：
3.4
作者：
BALDO, GJ;MATHIAS, RT
通讯作者：
MATHIAS, RT
影响因子：
4.1
作者：
HARDING, JJ;EGERTON, M;HARDING, RS
通讯作者：
HARDING, RS
影响因子：
3.3
作者：
Boswell, Bruce A.;Lein, Pamela J.;Musil, Linda S.
通讯作者：
Musil, Linda S.
影响因子：
4.8
作者：
Cheng, N;Chen, J
通讯作者：
Chen, J