title: Inhibitory effects of the transcription factor Ets-1 on the expression of type I collagen in TGF-β1-stimulated renal epithelial cells.
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.
authors: Department of Blood Purification, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan. kaokano@kc.twmu.ac.jp
authors: Kazuhiro
authors: K
authors: Okano
authors: Asako
authors: A
authors: Hibi
authors: Tokiko
authors: T
authors: Miyaoka
authors: Tomoko
authors: T
authors: Inoue
authors: Himiko
authors: H
authors: Sugimoto
authors: Ken
authors: K
authors: Tsuchiya
authors: Takashi
authors: T
authors: Akiba
authors: Kosaku
authors: K
authors: Nitta
mesh_terms: D002460:Cell Line; D024042:Collagen Type I / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D005109:Extracellular Matrix / Q000378:metabolism; D005355:Fibrosis / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D020935:MAP Kinase Signaling System; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism*; D051900:Smad3 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology
chemical_list: D024042:Collagen Type I; C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1