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. 2012 Oct;369(1-2):247-54. doi: 10.1007/s11010-012-1388-6. Epub 2012 Jul 25.

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.

MeSH terms

  • Cell Line
  • Collagen Type I / metabolism*
  • Epithelial Cells / metabolism
  • Epithelial-Mesenchymal Transition
  • Extracellular Matrix / metabolism
  • Fibrosis / metabolism
  • Humans
  • Kidney* / cytology
  • Kidney* / metabolism
  • MAP Kinase Signaling System
  • Proto-Oncogene Protein c-ets-1 / metabolism*
  • Smad3 Protein / antagonists & inhibitors
  • Smad3 Protein / metabolism
  • Transforming Growth Factor beta1* / metabolism
  • Transforming Growth Factor beta1* / pharmacology

Substances

  • Collagen Type I
  • ETS1 protein, human
  • Proto-Oncogene Protein c-ets-1
  • SMAD3 protein, human
  • Smad3 Protein
  • Transforming Growth Factor beta1