Induction of apoptosis by Smad3 and down-regulation of Smad3 expression in response to TGF-β in human normal lung epithelial cells

Kiyoshi Yanagisawa, Hirotaka Osada, Akira Masuda, Masashi Kondo, Toshiko Saito, Yasushi Yatabe, Kenzo Takagi, Toshitada Takahashi, Takashi Takahashi

Research output: Contribution to journalArticle

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Abstract

Smad family members are essential intracellular signaling components of the transforming growth factor-beta (TGF-β) superfamily involved in a range of biological activities. Two highly homologous molecules, Smad2 and Smad3, have so far been identified as receptor-activated Smads for TGF-β signaling and have become the focus of intensive studies. However, no definite differences in regulation or function have been established between these TGF-β signaling molecules. In the present study, we show that the expression of Smad3, but not its dose relative, Smad2, is down-regulated by TGF-β mediated signals themselves in human lung epithelial cells. This down-regulation of Smad3 by TGF-β treatment did not appear to result from shortening of the half-life of Smad3 mRNA. Constitutive expression of Smad3 in the presence of TGF-β induced apoptotic cell death, with an adverse effect on the cell growth of human lung epithelial cells. Apoptotic cell death could also be induced by forced expression of Smad2 in the presence of TGF-β, but less efficiently than by that of Smad3. These findings clearly define the distinctions between Smad2 and Smad3 for the first time in that a qualitative difference was observed with regard to the regulation of their expression in response to TGF-β, while Smad2 and Smad3 appeared to have quantitatively different capabilities regarding the induction of apoptotic cell death in human lung epithelial cells.

Original languageEnglish
Pages (from-to)1743-1747
Number of pages5
JournalOncogene
Volume17
Issue number13
DOIs
Publication statusPublished - 01-10-1998

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Transforming Growth Factor beta
Down-Regulation
Epithelial Cells
Apoptosis
Lung
Cell Death
Half-Life
Messenger RNA
Growth

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Yanagisawa, Kiyoshi ; Osada, Hirotaka ; Masuda, Akira ; Kondo, Masashi ; Saito, Toshiko ; Yatabe, Yasushi ; Takagi, Kenzo ; Takahashi, Toshitada ; Takahashi, Takashi. / Induction of apoptosis by Smad3 and down-regulation of Smad3 expression in response to TGF-β in human normal lung epithelial cells. In: Oncogene. 1998 ; Vol. 17, No. 13. pp. 1743-1747.
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Yanagisawa, K, Osada, H, Masuda, A, Kondo, M, Saito, T, Yatabe, Y, Takagi, K, Takahashi, T & Takahashi, T 1998, 'Induction of apoptosis by Smad3 and down-regulation of Smad3 expression in response to TGF-β in human normal lung epithelial cells', Oncogene, vol. 17, no. 13, pp. 1743-1747. https://doi.org/10.1038/sj.onc.1202052

Induction of apoptosis by Smad3 and down-regulation of Smad3 expression in response to TGF-β in human normal lung epithelial cells. / Yanagisawa, Kiyoshi; Osada, Hirotaka; Masuda, Akira; Kondo, Masashi; Saito, Toshiko; Yatabe, Yasushi; Takagi, Kenzo; Takahashi, Toshitada; Takahashi, Takashi.

In: Oncogene, Vol. 17, No. 13, 01.10.1998, p. 1743-1747.

Research output: Contribution to journalArticle

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