The roles of αV integrins in lens EMT and posterior capsular opacification.
The roles of αV integrins in lens EMT and posterior capsular opacification.
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DOI：
10.1111/jcmm.12213
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发表时间：
2014-04
影响因子：
5.3
通讯作者：
Duncan MK
中科院分区：
文献类型：
--
作者：
Mamuya FA;Wang Y;Roop VH;Scheiblin DA;Zajac JC;Duncan MK
后囊膜混浊是白内障手术后的主要并发症。当手术（LC）后剩余的透镜上皮细胞发生伤口愈合反应，产生表达α-平滑肌肌动蛋白（α-SMA）的肌成纤维细胞和透镜纤维细胞的混合物时，就会发生PCO，这会损害视力。先前的研究已经提出整合素在PCO中起核心作用，并且我们发现，在白内障手术的小鼠纤维细胞去除模型中，αV整合素及其相互作用的β亚基β1、β5、β6、β8的表达在手术后LC中与α-SMA一起上调。为了验证αV整合素在PCO发病机制中功能重要的假设，我们建立了所有透镜细胞中缺乏αV整合素亚基的小鼠。缺乏αV整联蛋白的成人晶状体是透明的，与对照晶状体相比，未显示明显的形态学异常。然而，在手术纤维细胞去除后，对照眼中的LC增加细胞增殖，并在48小时内上调α-SMA、β1-整联蛋白、纤连蛋白、腱生蛋白-C和转化生长因子β（TGF-β）诱导蛋白的表达，而缺乏αV整联蛋白的LC表现出更少的细胞增殖，并且几乎没有上调任何测试的纤维化标志物。这种效应似乎是由于α V整联蛋白在潜在TGF-β活化中的已知作用所致，因为αV整联蛋白无效晶状体在手术后未表现出可检测的SMAD-3磷酸化，而这在对照晶状体中强烈发生，与TGF-β在纤维化PCO中的已知作用一致。这些数据表明，拮抗αV整合素功能的治疗剂可用于预防白内障手术后的纤维化PCO。
Posterior capsular opacification (PCO) is the major complication arising after cataract treatment. PCO occurs when the lens epithelial cells remaining following surgery (LCs) undergo a wound healing response producing a mixture of α-smooth muscle actin (α-SMA)-expressing myofibroblasts and lens fibre cells, which impair vision. Prior investigations have proposed that integrins play a central role in PCO and we found that, in a mouse fibre cell removal model of cataract surgery, expression of αV integrin and its interacting β-subunits β1, β5, β6, β8 are up-regulated concomitant with α-SMA in LCs following surgery. To test the hypothesis that αV integrins are functionally important in PCO pathogenesis, we created mice lacking the αV integrin subunit in all lens cells. Adult lenses lacking αV integrins are transparent and show no apparent morphological abnormalities when compared with control lenses. However, following surgical fibre cell removal, the LCs in control eyes increased cell proliferation, and up-regulated the expression of α-SMA, β1-integrin, fibronectin, tenascin-C and transforming growth factor beta (TGF-β)–induced protein within 48 hrs, while LCs lacking αV integrins exhibited much less cell proliferation and little to no up-regulation of any of the fibrotic markers tested. This effect appears to result from the known roles of αV integrins in latent TGF-β activation as αV integrin null lenses do not exhibit detectable SMAD-3 phosphorylation after surgery, while this occurs robustly in control lenses, consistent with the known roles for TGF-β in fibrotic PCO. These data suggest that therapeutics antagonizing αV integrin function could be used to prevent fibrotic PCO following cataract surgery.
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DOI：
10.1158/1541-7786.mcr-11-0311
发表时间：
2011-11
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Augoff K;Das M;Bialkowska K;McCue B;Plow EF;Sossey-Alaoui K
通讯作者：
Sossey-Alaoui K
影响因子：
64.5
作者：
Brooks, PC;Stromblad, S;Cheresh, DA
通讯作者：
Cheresh, DA
影响因子：
3.4
作者：
Call, MK;Grogg, MW;Tsonis, PA
通讯作者：
Tsonis, PA
影响因子：
2
作者：
Barbour, W;Saika, S;Ohnishi, Y
通讯作者：
Ohnishi, Y
影响因子：
4.4
作者：
Dawes, Lucy Jean;Sleeman, Matthew Alexander;Wormstone, Ian Michael
通讯作者：
Wormstone, Ian Michael