Inhibitory effects of the transcription factor Ets-1 on the expression of type I collagen in TGF-β1-stimulated renal epithelial cells

被引:20
作者
Okano, Kazuhiro [1 ,2 ]
Hibi, Asako [2 ]
Miyaoka, Tokiko [1 ]
Inoue, Tomoko [1 ]
Sugimoto, Himiko [1 ]
Tsuchiya, Ken [1 ,2 ]
Akiba, Takashi [2 ]
Nitta, Kosaku [1 ]
机构
[1] Tokyo Womens Med Univ, Dept Med, Kidney Ctr, Shinjuku Ku, Tokyo 1628666, Japan
[2] Tokyo Womens Med Univ, Dept Blood Purificat, Kidney Ctr, Tokyo 1628666, Japan
关键词
TGF-beta; 1; Smad; Collagen; Ets-1; Renal cell; BETA TGF-BETA; GENE-EXPRESSION; MESENCHYMAL TRANSITION; SIGNALING PATHWAY; COOPERATION; PROTOONCOGENE; STIMULATION; PROTEINS; RAS; SP1;
D O I
10.1007/s11010-012-1388-6
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Extracellular matrix (ECM) production and epithelial-mesenchymal transition (EMT) are important for phenotypic conversion in normal development and disease states such as tissue fibrosis. Transforming growth factor-beta 1 (TGF beta 1) is one of the most potent inducers of ECM proteins, and its role in the pathogenesis of fibrosis is well established. Ets family is involved in a diverse array of biologic functions including cellular growth, migration, and differentiation. In the present study, we investigated whether Ets-1 has a role in ECM production and EMT in human renal tubuloepithelial cells (HKC cells). TGF beta 1 treatment increases Ets-1 expression and nuclear translocation in the HKC cells. Overexpression of recombinant Ets-1 suppressed transcription of alpha 2(I) collagen (COL1A2) and type I collagen production in the TGF beta 1-activated HKC cells. From the experiments using specific inhibitors against Smad3 or mitogen-activated protein (MAP) kinase pathways, Ets-1 has an inhibitory role for COL1A2 transcription and the p38 MAPK pathway participates in the negative contribution of Ets-1 in TGF beta 1/Smad3-activated renal cells.
引用
收藏
页码:247 / 254
页数:8
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