Sp1 mediates microRNA-29c-regulated type I collagen production in renal tubular epithelial cells
Sp1 mediates microRNA-29c-regulated type I collagen production in renal tubular epithelial cells
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Sp1 介导肾小管上皮细胞中 microRNA-29c 调节的 I 型胶原蛋白产生。
DOI：
10.1016/j.yexcr.2013.06.007
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发表时间：
2013-08-15
影响因子：
3.7
通讯作者：
He, Weichun
中科院分区：
文献类型：
--
作者：
Jiang, Lei;Zhou, Yang;He, Weichun
特异性蛋白1（SpecificityProtein 1，Sp1）是一种广泛表达的转录因子，通过调控多种纤维化相关基因的表达，在多种器官纤维化疾病中发挥潜在的致病作用，但其在肾纤维化中的作用及其调控机制尚不完全清楚。在这里，我们发现，Sp1显着诱导和密切相关的间质I型胶原积累在肾小管上皮细胞阻塞性肾病。在体外实验中，TGF-β 1处理的肾小管上皮细胞（NRK-52 E）中，Sp1和I型胶原蛋白的表达均上调，而Sp1的敲低在很大程度上消除了TGF-β 1诱导的I型胶原蛋白的产生，这表明Sp1诱导部分负责I型胶原蛋白的表达。此外，我们发现miR-29 c的表达在DUO肾病的肾小管上皮细胞或TGF-β 1处理的NRK-52 E细胞中显著降低。在NRK-52 E细胞中，miR-29 c的敲低可充分诱导Sp1和I型胶原的表达，而miR-29 c的异位表达在很大程度上消除了TGF-β 1刺激的它们的表达。此外，Sp1的敲低有效地阻碍了由miR-29 c下调刺激的I型胶原诱导。总的来说，这项研究表明，Sp1作为一个重要的调解人的miR-29 c在调节I型胶原蛋白的产生在肾小管上皮细胞，这可能提供了一个新的机制的见解miR-29 c在肾纤维化。(C)2013 Elsevier Inc. All rights reserved.
Specificity protein 1 (Sp1), a ubiquitously expressed transcription factor, plays a potential pathogenic role for fibrotic disease in many organs by regulating the expression of several fibrosis-related genes, however, its role in kidney fibrosis and the mechanisms regulating its expression remain incompletely clarified. Here, we found that Sp1 was markedly induced and closely correlated with interstitial type I collagen accumulation in kidney tubular epithelia from obstructive nephropathy. In vitro, both Sp1 and type I collagen expression were up-regulated in TGF-beta 1-treated kidney tubular epithelial cells (NRK-52E), whereas knockdown of Sp1 largely abolished TGF-beta 1-induced type I collagen production, suggesting that Sp1 induction is partially responsible for type I collagen expression. In addition, we found that miR-29c expression was remarkably reduced in either the tubular epithelial cells from kidney with DUO nephropathy or TGF-beta 1-treated NRK-52E cells. Knockdown of miR-29c could sufficiently induce Sp1 and type I collagen expression, whereas ectopic expression of miR-29c largely abolished their expression stimulated by TGF-beta 1 in NRK-52E cells. Furthermore, knockdown of Sp1 effectively hindered type I collagen induction stimulated by miR-29c down-regulation. Collectively, this study demonstrates that Sp1 acts as an essential mediator for miR-29c in regulating type I collagen production in tubular epithelial cells, which may provide a novel mechanistic insight about miR-29c in renal fibrosis. (C) 2013 Elsevier Inc. All rights reserved.