Role of Decorin in Posterior Capsule Opacification and Eye Lens Development.
Role of Decorin in Posterior Capsule Opacification and Eye Lens Development.
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作者：
Shibata S;Shibata N;Ohtsuka S;Yoshitomi Y;Kiyokawa E;Yonekura H;Singh DP;Sasaki H;Kubo E
核心蛋白聚糖（DCN）参与多种生理和病理过程。透镜上皮细胞（LECs）的上皮-间充质转化（EMT）被认为是白内障手术后后囊膜混浊（PCO）发生的主要原因。我们研究了抑制PCO的可能的靶基因。使用基于微阵列的方法，与对照组相比，大鼠PCO组织中Dcn的表达显著上调。用成纤维细胞生长因子（FGF）2处理的LEC显示DCN表达水平增加，而用转化生长因子（TGF）β-2处理的LEC显示DCN表达降低。加入TGFβ 2后，透镜EMT的标志物原肌球蛋白1（Tpm 1）的表达增加，而在过表达人DCN（hDCN）的人LEC中，Tpm 1 mRNA或蛋白表达的上调减少。在8周龄和48周龄转基因小鼠晶状体特异性hDCN（hDCN-Tg）中未观察到表型变化。在hDCN-Tg小鼠晶状体中，损伤诱导的小鼠透镜的EMT和α平滑肌肌动蛋白的表达模式减弱。在透镜的伤口愈合过程中观察到，过表达DCN抑制TGFβ 2诱导的Tpm 1和EMT的上调，但直到48周龄才影响小鼠透镜的形态。我们的研究结果表明，DCN在调节LEC和PCO的EMT形成中起着重要作用，并表明对于治疗干预，维持DCN的生理表达对于减弱EMT进展和PCO形成至关重要。
Decorin (DCN) is involved in a variety of physiological and pathological processes. Epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) has been proposed as a major cause for the development of posterior capsule opacification (PCO) after cataract surgery. We investigated the plausible target gene(s) that suppress PCO. The expression of Dcn was significantly upregulated in rat PCO tissues compared to that observed in the control using a microarray-based approach. LECs treated with fibroblast growth factor (FGF) 2 displayed an enhanced level of DCN expression, while LECs treated with transforming growth factor (TGF)β-2 showed a decrease in DCN expression. The expression of tropomyosin 1 (Tpm1), a marker of lens EMT increased after the addition of TGFβ-2 in human LEC; however, upregulation of Tpm1 mRNA or protein expression was reduced in human LECs overexpressing human DCN (hDCN). No phenotypic changes were observed in the lenses of 8- and 48-week-old transgenic mice for lens-specific hDCN (hDCN-Tg). Injury-induced EMT of the mouse lens, and the expression patterns of α smooth muscle actin, were attenuated in hDCN-Tg mice lenses. Overexpression of DCN inhibited the TGFβ-2-induced upregulation of Tpm1 and EMT observed during wound healing of the lens, but it did not affect mouse lens morphology until 48 weeks of age. Our findings demonstrate that DCN plays a significant role in regulating EMT formation of LECs and PCO, and suggest that for therapeutic intervention, maintenance of physiological expression of DCN is essential to attenuate EMT progression and PCO formation.
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影响因子：
5.3
作者：
Kubo E;Hasanova N;Fatma N;Sasaki H;Singh DP
通讯作者：
Singh DP
影响因子：
64.8
作者：
BORDER, WA;NOBLE, NA;RUOSLAHTI, E
通讯作者：
RUOSLAHTI, E
影响因子：
3.4
作者：
Davies, JE;Tang, XF;Davies, SJA
通讯作者：
Davies, SJA
影响因子：
4.6
作者：
D'Antin JC;Barraquer RI;Tresserra F;Michael R
通讯作者：
Michael R
影响因子：
5.3
作者：
Kubo E;Shibata S;Shibata T;Kiyokawa E;Sasaki H;Singh DP
通讯作者：
Singh DP