Requirement of Smad3 for mast cell growth

Masayuki Funaba, Kohei Nakaya, Teruo Ikeda, Masaru Murakami, Kunihiro Tsuchida, Hiromu Sugino

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10 Citations (Scopus)

Abstract

The involvement of the TGF-β family in cell growth of bone marrow-derived mast cells (BMMC) cultured with medium containing pokeweed mitogen-stimulated spleen cell-conditioned medium (PWM-SCM) was examined. Doubling time of BMMC from Smad3-null mice was longer than that from wild-type (WT) mice, and the differences tended to be larger with time of culture. Consistent with the results, uptake and reduction of [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt; MTS] was lower in Smad3-deficient BMMC. Cell cycle analyses revealed no apparent differences between WT BMMC and Smad3-deficient BMMC, suggesting that longer doubling time in Smad3-deficient BMMC resulted from increased cell death. TGF-β and activin A were supplied by PWM-SCM rather than by self-production by BMMC. Blocking the TGF-β pathway by anti-TGF-β neutralizing antibody or an inhibitor for the type I receptors for ligands including TGF-β and activin, SB431542, inhibited MTS uptake and reduction in WT BMMC, whereas anti-activin A antibody and SB431542 tended to inhibit them in Smad3-deficient BMMC. The present results suggest that TGF-β-induced and Smad3-mediated signaling is essential for maximal cell growth in mast cells, and that the activin pathway may be required for it when mast cell context is modulated by Smad3 depletion.

Original languageEnglish
Pages (from-to)47-52
Number of pages6
JournalCellular Immunology
Volume240
Issue number1
DOIs
Publication statusPublished - 01-03-2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology

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    Funaba, M., Nakaya, K., Ikeda, T., Murakami, M., Tsuchida, K., & Sugino, H. (2006). Requirement of Smad3 for mast cell growth. Cellular Immunology, 240(1), 47-52. https://doi.org/10.1016/j.cellimm.2006.06.002