Aging-dependent loss of GAP junction proteins Cx46 and Cx50 in the fiber cells of human and mouse lenses accounts for the diminished coupling conductance.
Aging-dependent loss of GAP junction proteins Cx46 and Cx50 in the fiber cells of human and mouse lenses accounts for the diminished coupling conductance.
复制标题
人和小鼠晶状体纤维细胞中 GAP 连接蛋白 Cx46 和 Cx50 的老化依赖性损失导致耦合电导减弱
DOI：
10.18632/aging.203247
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发表时间：
2021-07-04
期刊：
影响因子：
--
通讯作者：
Li DW
中科院分区：
文献类型：
--
作者：
Gong XD;Wang Y;Hu XB;Zheng SY;Fu JL;Nie Q;Wang L;Hou M;Xiang JW;Xiao Y;Gao Q;Bai YY;Liu YZ;Li DW
通过缝隙连接通道传播的微循环系统维持了晶状体的内稳态。众所周知，晶状体的细胞间通讯在老化过程中会恶化。然而，人类晶状体这种变化的分子基础还没有很好地确定。在这里，我们提出的证据表明，超过90%的Cx46和CX50在50岁及以上的正常人晶状体纤维细胞中丢失。从透明晶状体到白内障晶状体，Cx43在晶状体上皮细胞中表达上调，Cx46和CX50在晶状体上皮细胞中表达下调。在小鼠晶状体老化过程中，Cx43没有变化，但Cx46和CX50的表达均显著下调。在氧化应激处理下，小鼠晶状体在体外发生白内障。与此过程相关的是，Cx43显著上调，而Cx46和CX50则显著下调。总之，我们的结果首次揭示了Cx46和CX50水平的下调似乎是偶联电导降低的主要原因，而Cx46和CX50的衰老相关性丢失促进了老年性白内障的发生。
The homeostasis of the ocular lens is maintained by a microcirculation system propagated through gap junction channels. It is well established that the intercellular communications of the lens become deteriorative during aging. However, the molecular basis for this change in human lenses has not been well defined. Here, we present evidence to show that over 90% of Cx46 and Cx50 are lost in the fiber cells of normal human lenses aged 50 and above. From transparent to cataractous lenses, while Cx43 was upregulated, both Cx46 and Cx50 were significantly down-regulated in the lens epithelia. During aging of mouse lenses, Cx43 remained unchanged, but both Cx46 and Cx50 were significantly downregulated. Under oxidative stress treatment, mouse lenses develop in vitro cataractogenesis. Associated with this process, Cx43 was significantly upregulated, in contrast, Cx46 and Cx50 were sharply downregulated. Together, our results for the first time reveal that downregulation in Cx46 and Cx50 levels appears to be the major reason for the diminished coupling conductance, and the aging-dependent loss of Cx46 and Cx50 promotes senile cataractogenesis.
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