Epithelial-mesenchymal transition as a therapeutic target for prevention of ocular tissue fibrosis
Epithelial-mesenchymal transition as a therapeutic target for prevention of ocular tissue fibrosis
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DOI：
10.2174/187153008783928343
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发表时间：
2008-03-01
影响因子：
1.9
通讯作者：
Ikeda, Kazuo
中科院分区：
文献类型：
--
作者：
Saika, Shizuya;Yamanaka, Osamu;Ikeda, Kazuo
纤维化疾病的特征在于肌成纤维细胞（参与纤维化反应的关键细胞类型）的出现，以及细胞外基质的过度积累，导致组织收缩和功能受损。肌成纤维细胞通过成纤维细胞-肌成纤维细胞转化产生，并且在某些组织中通过上皮-间充质转化（EMT）产生，上皮细胞通过EMT改变其表型以变得更像间充质细胞的过程。虽然由损伤组织产生的炎性/纤维化生长因子/细胞因子协调EMT的过程，但转化生长因子β（TGF β）被认为在该过程中起核心作用。与其中肌成纤维细胞由成纤维细胞和上皮细胞产生的肾或其它组织中的纤维化病变不同，眼睛晶状体透镜中的纤维化病变仅来源于透镜上皮细胞，而不污染成纤维细胞来源的肌成纤维细胞。因此，该组织适合于研究EMT和随后的组织纤维化的详细机制。视网膜色素上皮细胞中的EMT参与另一种眼部纤维化疾病，增殖性玻璃体视网膜病变（一种视网膜纤维化）的发展。EMT相关的信号转导级联，即，TGF β/Smad是预防或治疗不利的眼组织纤维化的靶点，例如，在一个实施例中，晶状体透镜或视网膜以及可能的其它器官中的纤维变性疾病。
Fibrotic diseases are characterized by the appearance of myofibroblasts, the key cell type involved in the fibrogenic reaction, and by excess accumulation of extracellular matrix with resultant tissue contraction and impaired function. Myofiborblasts are generated by fibroblast-myofibrobalst conversion, and in certain tissues through epithelial-mesenchymal transition (EMT), a process through which an epithelial cell changes its phenotype to become more like a mesenchymal cell. Although inflammatory/fibrogenic growth factors/cytokines produced by injured tissues orchestrate the process of EMT, transforming growth factor beta(TGF beta) is believed to play a central role in the process. Unlike fibrotic lesions in kidney or other tissues where myofibroblasts are generated from both fibroblasts and epithelial cells, fibrotic lesions in the eye crystalline lens are derived only from lens epithelial cells without contamination of fibroblast-derived myofibroblasts. Thus, this tissue is suitable to investigate detailed mechanisms of EMT and subsequent tissue fibrosis. EMT in retinal pigment epithelium is involved in the development of another ocular fibrotic disease, proliferative vitreo-retinopathy, a fibrosis in the retina. EMT-related signal transduction cascades, i.e., TGF beta/Smad, are a target to prevent or treat unfavorable ocular tissue fibrosis, e. g., fibrotic diseases in the crystalline lens or retina, as well as possibly in other organs.