Elevated tropomyosin expression is associated with epithelial-mesenchymal transition of lens epithelial cells.
Elevated tropomyosin expression is associated with epithelial-mesenchymal transition of lens epithelial cells.
复制标题
DOI：
10.1111/j.1582-4934.2012.01654.x
复制
发表时间：
2013-01
影响因子：
5.3
通讯作者：
Singh DP
中科院分区：
文献类型：
--
作者：
Kubo E;Hasanova N;Fatma N;Sasaki H;Singh DP
晶状体上皮细胞（LECs）损伤导致上皮-间质转化（EMT），并导致纤维化。原肌球蛋白（Tpm）家族的细胞骨架蛋白参与调节和稳定肌动蛋白微丝。Tpms的异常表达会导致细胞形态的异常变化，并导致上皮完整性的破坏。LECs的EMT被认为是白内障术后后囊膜混浊（PCO）的主要原因。通过啮齿类动物PCO和人白内障LECs，我们证实了大鼠Tpm和人Tpm1α/2β的异常表达表明它们与LECs EMT过程中肌动蛋白细胞骨架的重塑有关。晶状体摘除术后异常生长的lec的表达分析显示，EMT的标志物α-平滑肌肌动蛋白（α-SMA）表达升高。重要的是，这些细胞在EMT/PCO形成后显示出Tpm1α/2β的表达增加。与非白内障大鼠相比，蜀谷白内障大鼠晶状体上皮细胞中Tpm1α/2β的表达上调。此外，人类核性白内障和前囊下纤维化（ASF）患者的LECs中Tpm2β mRNA的表达显著增加，这表明类似的信号在白内障SCR和人类晶状体的LECs中调用这些分子的表达。在Tpm1α/2β过表达的LECs中观察到EMT， α-SMA表达增加。这些情况与肌动蛋白丝的重塑有关，可能导致EMT/PCO和ASF。本研究结果可能有助于阐明EMT形态发生过程中肌动蛋白细胞骨架的状况，并可能有助于开发基于tpm的抑制剂，以延缓PCO和白内障的发生。
Injury to lens epithelial cells (LECs) leads to epithelial–mesenchymal transition (EMT) with resultant fibrosis. The tropomyosin (Tpm) family of cytoskeleton proteins is involved in regulating and stabilizing actin microfilaments. Aberrant expression of Tpms leads to abnormal morphological changes with disintegration of epithelial integrity. The EMT of LECs has been proposed as a major cause of posterior capsule opacification (PCO) after cataract surgery. Using in vivo rodent PCO and human cataractous LECs, we demonstrated that the aberrant expression of rat Tpm and human Tpm1α/2β suggested their association in remodelling of the actin cytoskeleton during EMT of LECs. Expression analysis from abnormally growing LECs after lens extraction revealed elevated expression of α-smooth muscle actin (α-SMA), a marker for EMT. Importantly, these cells displayed increased expression of Tpm1α/2β following EMT/PCO formation. Expression of Tpm1α/2β was up-regulated in LECs isolated from cataractous lenses of Shumiya Cataract Rats (SCRs), compared with non-cataractous lenses. Also, LECs from human patients with nuclear cataract and anterior subcapsular fibrosis (ASF) displayed significantly increased expression of Tpm2β mRNA, suggesting that similar signalling invokes the expression of these molecules in LECs of cataractous SCR and human lenses. EMT was observed in LECs overexpressed with Tpm1α/2β, as evidenced by increased expression of α-SMA. These conditions were correlated with remodelling of actin filaments, possibly leading to EMT/PCO and ASF. The present findings may help clarify the condition of the actin cytoskeleton during morphogenetic EMT, and may contribute to development of Tpm-based inhibitors for postponing PCO and cataractogenesis.
登录
查看更多内容
影响因子：
64.8
作者：
BORDER, WA;NOBLE, NA;RUOSLAHTI, E
通讯作者：
RUOSLAHTI, E
影响因子：
4.4
作者：
Junn, E;Lee, KN;Choi, I
通讯作者：
Choi, I
影响因子：
2.9
作者：
Fatma N;Kubo E;Sen M;Agarwal N;Thoreson WB;Camras CB;Singh DP
通讯作者：
Singh DP
影响因子：
3.4
作者：
De Iongh, RU;Gordon-Thomson, C;McAvoy, JW
通讯作者：
McAvoy, JW
影响因子：
19.6
作者：
Iglesias-de la Cruz, MC;Ruiz-Torres, P;Rodríguez-Puyol, D
通讯作者：
Rodríguez-Puyol, D