Lens transcriptome profile during cataract development in Mip-null mice.
Lens transcriptome profile during cataract development in Mip-null mice.
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DOI：
10.1016/j.bbrc.2016.08.068
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发表时间：
2016-09-16
影响因子：
3.1
通讯作者：
Shiels A
中科院分区：
文献类型：
--
作者：
Bennett TM;Zhou Y;Shiels A
主要内在蛋白或水通道蛋白0（MIP/AQP 0）在脊椎动物眼透镜中作为水通道和细胞连接分子起作用。透镜中MIP功能的丧失导致光学质量下降和白内障形成，其致病机制尚不清楚。在这里，我们使用微阵列杂交分析来检测白内障形成过程中的透镜转录组变化，这些小鼠的MIP（Mip−/−）功能无效。在新生儿Mip−/−晶状体（P1）中，11个基因上调，18个基因下调（>2倍，p=<0.05），在P7时，相似数量的基因差异表达。P1时Mip−/−透镜中上调最多（>6倍）的基因包括编码线粒体转位酶（Timmdc 1）、基质金属肽酶（Mmp 2）、Rho GTP酶相互作用蛋白（Ubxn 11）和转录因子（Twist 2）的基因。除了Mip，P1时Mip−/−透镜中下调最多（>4倍）的基因包括编码蛋白酶体亚单位（Psmd 8）、核糖核酸酶（Pop 4）和热休克蛋白（Hspb 1）的基因。Mip−/−透镜中的透镜纤维细胞变性与TUNEL阳性细胞核数量增加和钙蛋白酶介导的α II-血影蛋白蛋白水解水平显著升高相关。然而，通过谷胱甘肽和自由基水平测量的红牛状态与野生型相似。这些数据表明，虽然在Mip−/−透镜中相对较少的基因（约1.5%的转录组）差异调节>2倍，但钙蛋白酶超活化在透镜纤维细胞死亡和白内障形成期间充当终末致病事件。
Major intrinsic protein or aquaporin-0 (MIP/AQP0) functions as a water channel and a cell-junction molecule in the vertebrate eye lens. Loss of MIP function in the lens leads to degraded optical quality and cataract formation by pathogenic mechanisms that are unclear. Here we have used microarray-hybridization analysis to detect lens transcriptome changes during cataract formation in mice that are functionally null for MIP (Mip−/−). In newborn Mip−/− lenses (P1) 11 genes were up-regulated and 18 were down-regulated (>2-fold, p=<0.05) and a similar number of genes was differentially regulated at P7. The most up-regulated genes (>6-fold) in the Mip−/− lens at P1 included those coding for a mitochondrial translocase (Timmdc1), a matrix metallopeptidase (Mmp2), a Rho GTPase-interacting protein (Ubxn11) and a transcription factor (Twist2). Apart from Mip, the most down-regulated genes (>4-fold) in the Mip−/− lens at P1 included those coding for a proteasome sub-unit (Psmd8), a ribonuclease (Pop4), and a heat-shock protein (Hspb1). Lens fiber cell degeneration in the Mip−/− lens was associated with increased numbers of TUNEL-positive cell nuclei and dramatically elevated levels of calpain-mediated proteolysis of αII-spectrin. However red-ox status, measured by glutathione and free-radical levels, was similar to that of wild-type. These data suggest that while relatively few genes (~1.5% of the transcriptome) were differentially regulated >2-fold in the Mip−/− lens, calpain hyper-activation acts as a terminal pathogenic event during lens fiber cell death and cataract formation.
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影响因子：
5
作者：
Huang, Jing;Guo, Jian;Beigi, Farideh;Hodgkinson, Conrad P.;Facundo, Heberty T.;Zhang, Zhiping;Espinoza-Derout, Jorge;Zhou, Xiyou;Pratt, Richard E.;Mirotsou, Maria;Dzau, Victor J.
通讯作者：
Dzau, Victor J.
影响因子：
3.7
作者：
Aziz, Azhari;Harrop, Sean P.;Bishop, Naomi E.
通讯作者：
Bishop, Naomi E.
影响因子：
2
作者：
Bermudez, Maria A.;Vicente, Ana F.;Gonzalez, Francisco
通讯作者：
Gonzalez, Francisco
影响因子：
4.8
作者：
Ho, YS;Xiong, Y;Ho, DS
通讯作者：
Ho, DS
影响因子：
3.4
作者：
Sakamoto-Mizutani, K;Fukiage, C;Shearer, TR
通讯作者：
Shearer, TR