TGFβ stimulated re-epithelialisation is regulated by CTGF and Ras/MEK/ERK signalling
TGFβ stimulated re-epithelialisation is regulated by CTGF and Ras/MEK/ERK signalling
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DOI：
10.1016/j.yexcr.2007.09.001
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发表时间：
2008-01-01
影响因子：
3.7
通讯作者：
Daniels, Julie T.
中科院分区：
文献类型：
--
作者：
Secker, Genevieve A.;Shortt, Alex J.;Daniels, Julie T.
转化生长因子β（TGF β）调节复层上皮损伤后上皮再生的复杂机制尚未完全了解。TGF β通过结合不同的受体激活下游效应物，包括启动靶基因转录的Smads来发出信号。然而，研究表明，TGF β也可以通过MAPK途径独立于Smads发出信号，证明了TGF β信号的多样性。结缔组织生长因子（CTGF）由TGF β强烈诱导并在TGF β下游起作用，通过诱导基质沉积、成纤维细胞转化为收缩性肌成纤维细胞（例如真皮和角膜基质）和刺激上皮-间充质转化（例如肾和肺）引起组织中的病理生理学，所有这些已知引起纤维化。然而，CTGF在上皮细胞功能中的作用并不涉及对纤维化的直接贡献，尚未得到证实。我们首次表明，CTGF在人角膜上皮细胞培养物中的合成是由TGF β通过Ras/MEK/ERK MAPK信号通路诱导的，并且这是通过细胞迁移发生再上皮化所必需的。这些数据揭示了CTGF在调节上皮组织修复中的新功能，超出了其在纤维化中的既定作用，并进一步强调了TGF β调节上皮细胞功能的复杂性。(C)2007年爱思唯尔公司All rights reserved.
The complex mechanisms by which transforming growth factor beta (TGF beta) regulate re-epithelialisation following injury of stratified epithelia are not fully understood. TGF beta signals via binding to distinct receptors activating downstream effectors, including Smads which initiate transcription of target genes. However, studies have shown that TGF beta can also signal independently of Smads through MAPK pathways, demonstrating the diversity of TGF beta signalling. Connective tissue growth factor (CTGF) is strongly induced by and acts downstream of TGF beta causing pathophysiology in tissues by inducing matrix deposition, conversion of fibroblasts into contractile myofibroblasts (e.g. dermis and corneal stroma) and stimulation of epithelial-to-mesenchymal transition (e.g. kidney and lung) all of which are known to cause fibrosis. However, a role for CTGF in epithelial cell function which does not involve direct contribution to fibrosis has not been demonstrated. We show for the first time that synthesis of CTGF in cultures of human corneal epithelial cells is induced by TGF beta through the Ras/MEK/ERK MAPK signalling pathway and that this is required for re-epithelialisation to occur through cell migration. These data reveal a novel function for CTGF in the regulation of epithelial tissue repair beyond its established role in fibrosis, and further highlight the complexity of TGF beta regulation of epithelial cell function. (C) 2007 Elsevier Inc. All rights reserved.