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

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Abstract

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-β1 (TGFβ1) 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). TGFβ1 treatment increases Ets-1 expression and nuclear translocation in the HKC cells. Overexpression of recombinant Ets-1 suppressed transcription of α2(I) collagen (COL1A2) and type I collagen production in the TGFβ1-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 TGFβ1/Smad3-activated renal cells.

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Disclosure

This study was not sponsored by any groups. We have no commercial conflict in connection with this study.

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Authors and Affiliations

  1. Department of Blood Purification, Kidney Center, Tokyo Women’s Medical University, Tokyo, Japan

    Kazuhiro Okano, Asako Hibi, Ken Tsuchiya & Takashi Akiba

  2. Department of Medicine, Kidney Center, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan

    Kazuhiro Okano, Tokiko Miyaoka, Tomoko Inoue, Himiko Sugimoto, Ken Tsuchiya & Kosaku Nitta

Authors
  1. Kazuhiro Okano
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  2. Asako Hibi
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  3. Tokiko Miyaoka
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  6. Ken Tsuchiya
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  8. Kosaku Nitta
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Correspondence to Kazuhiro Okano.

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ETS-1 increases TGF-β1-mediated renal fibrosis.

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Okano, K., Hibi, A., Miyaoka, T. et al. Inhibitory effects of the transcription factor Ets-1 on the expression of type I collagen in TGF-β1-stimulated renal epithelial cells. Mol Cell Biochem 369, 247–254 (2012). https://doi.org/10.1007/s11010-012-1388-6

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  • DOI: https://doi.org/10.1007/s11010-012-1388-6

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