Coordinated Regulation of Palladin and α-Smooth Muscle Actin by Transforming Growth Factor-β in Human Corneal Fibroblasts.
Coordinated Regulation of Palladin and α-Smooth Muscle Actin by Transforming Growth Factor-β in Human Corneal Fibroblasts.
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通过人角膜成纤维细胞中转化生长因子-β 协调调节 Palladin 和 α-平滑肌肌动蛋白。
DOI：
10.1167/iovs.15-18763
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Sonoda KH.
中科院分区：
文献类型：
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作者：
Morishige N;Murata S;Nakamura Y;Azumi H;Shin-Gyou-Uchi R;Oki KT;Morita Y;Sonoda KH.
目的：为了研究palladin在角膜中的作用，我们检测了这种肌动蛋白组装相关蛋白在正常、患病或损伤的角膜组织以及培养的角膜成纤维细胞中的表达。palladin和α-平滑肌肌动蛋白（α-SMA）在大鼠角膜切口伤、正常人角膜和病变人角膜中的表达，结果：在大鼠角膜创伤愈合过程中，palladin和α-SMA在损伤部位均有表达。尽管在正常人角膜中未检测到palladin或α-SMA，但在具有以存在纤维化为特征的潜在病症的患病人角膜中检测到两种蛋白质的共定位。转化生长因子-β（TGF-β）以一种对Smad或丝裂原活化蛋白激酶（MAPK）信号传导阻断剂抑制敏感的方式增加培养的人角膜成纤维细胞中palladin和α-SMA的表达。最后，RNA干扰介导的palladin耗竭减弱了TGF-β诱导的人角膜成纤维细胞中α-SMA表达的上调以及TGF-β诱导的这些细胞介导的胶原凝胶收缩。TGF-β以依赖于Smad和MAPK信号传导的方式增加人角膜成纤维细胞中palladin的表达，并且是TGF-β诱导的α-SMA上调所需的。
Purpose: To investigate the role of palladin in the cornea, we examined expression of this actin assembly–related protein in normal, diseased, or injured corneal tissue as well as in cultured corneal fibroblasts.Methods: Expression of palladin and α–smooth muscle actin (α-SMA) in the rat cornea with an incision wound, in the normal and diseased human cornea, and in cultured human corneal fibroblasts was examined by immunofluorescence or immunoblot analysis.Results: The expression of both palladin and α-SMA was detected at the lesion site during wound healing in the rat cornea. Whereas neither palladin nor α-SMA was detected in the normal human cornea, the colocalization of both proteins was detected in diseased human corneas with underlying conditions characterized by the presence of fibrosis. The expression of both palladin and α-SMA in cultured human corneal fibroblasts was increased by transforming growth factor–β (TGF-β) in a manner sensitive to inhibition by blockers of Smad or mitogen-activated protein kinase (MAPK) signaling. Finally, RNA interference–mediated depletion of palladin attenuated the TGF-β–induced upregulation of α-SMA expression in human corneal fibroblasts as well as TGF-β–induced collagen gel contraction mediated by these cells.Conclusions: Palladin is expressed in the rat and human cornea in association with scar formation. Expression of palladin in human corneal fibroblasts is increased by TGF-β in a manner dependent on Smad and MAPK signaling and is required for the TGF-β–induced upregulation of α-SMA.