Renal fibrosis -: Collagen composition and assembly regulates epithelial-mesenchymal transdifferentiation
Renal fibrosis -: Collagen composition and assembly regulates epithelial-mesenchymal transdifferentiation
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DOI：
10.1016/s0002-9440(10)62518-7
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发表时间：
2001-10-01
影响因子：
6
通讯作者：
Kalluri, R
中科院分区：
文献类型：
--
作者：
Zeisberg, M;Bonner, G;Kalluri, R
IV型胶原是基底膜的主要成分，它为各种细胞类型提供结构和功能支持。IV型胶原以高度复杂的上层结构形式存在，最近的研究表明，原聚体（IV型胶原的三聚体构建单元）的组装是由存在于每个胶原α -链多肽c端的NC1结构域介导的。在这里，我们发现IV型胶原有助于维持近端小管上皮的上皮表型。而I型胶原促进上皮向间充质转分化（EMT）。此外，重组人α - 1NC1结构域抑制IV型胶原NC1六聚体的组装，并可能破坏IV型胶原的沉积，促进体外EMT。α 1NC1结构域对W型胶原组装的抑制上调了近端小管上皮细胞中转化生长因子- β(1)的产生，这是EMT的诱导剂。这些结果强烈表明，基底膜结构对维持上皮表型至关重要，基底膜结构的变化可能导致转化生长因子- β的上调(1)，这有助于肾纤维化期间的EMT。
Type IV collagen is a major component of basement membranes and it provides structural and functional support to various cell types. Type IV collagen exists in a highly complex suprastructure form and recent studies implicate that protomer (the trimeric building unit of type IV collagen) assembly is mediated by the NC1 domain present in the C-terminus of each collagen alpha -chain polypeptide. Here we show that type IV collagen contributes to the maintenance of the epithelial phenotype of proximal tubular epithelial. cells, whereas type I collagen promotes epidielial-to-mesenchymal transdifferentiation (EMT). in addition, the recombinant human alpha 1NC1 domain inhibits assembly of type IV collagen NC1 hexamers and potentially disrupts the deposition of type IV collagen, facilitating EMT in vitro. Inhibition of type W collagen assembly by the alpha 1NC1 domain up-regulates the production of transforming growth factor-beta (1) in proximal tubular epithelial cells, an inducer of EMT. These results strongly suggest that basement membrane architecture is pivotal for the maintenance of epithelial phenotype and that changes in basement membrane architecture potentially lead to up-regulation of transforming growth factor-beta (1), which contributes to EMT during renal fibrosis.