Potential regulatory elements of the constitutive up-regulated α2(I) collagen gene in scleroderma dermal fibroblasts

Masatoshi Jinnin, Hironobu Ihn, Yoshihiro Mimura, Yoshihide Asano, Kunihiko Tamaki

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


The promoter activity of the full-length α2(I) collagen gene is higher in scleroderma fibroblasts, when compared to normal fibroblasts. In this study, to investigate the molecular mechanisms up-regulating the expression of the α2(I) collagen gene in scleroderma dermal fibroblasts more clearly, we compared promoter activities of serial 5′-deletion mutants and the substitution mutants of the α2(I) collagen promoter constructs between normal and scleroderma fibroblasts. The transient transfection assays using a series of 5′-deletions of the promoter revealed that the up-regulated fold-increase in scleroderma fibroblasts relative to that in normal fibroblasts was significantly decreased by the removal of bp -353 to -264 fragment or bp -264 to -186 fragment. The substitution mutations introduced into binding sites of Sp1 (bp -303 and -271), Ets1 (bp -285 and -282), as well as Smad (bp -263 and -258) also abrogated the fold-increase in promoter activity in scleroderma fibroblasts synergistically. A DNA affinity precipitation assay showed that the binding activity of Ets1 as well as Smad3 to their binding sites was increased in scleroderma fibroblasts compared with normal cells. Taken together, our promoter analysis emphasized that Ets1 form a transcriptionally active complex with Smad and Sp1 by autocrine transforming growth factor (TGF)-β signaling, leading to the intrinsic up-regulation of α2(I) collagen promoter activity in scleroderma fibroblasts. The blockade of autocrine TGF-β signaling is thought to be one of the most reliable approaches in the treatment of scleroderma, and further study targeting Ets1, Smad or Sp1 may contribute to this blockade.

Original languageEnglish
Pages (from-to)904-909
Number of pages6
JournalBiochemical and biophysical research communications
Issue number3
Publication statusPublished - 2006 May 12
Externally publishedYes


  • Extracellular matrix
  • Fibrosis
  • Transcription factor
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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