Requirement of Smad3 for mast cell growth
Requirement of Smad3 for mast cell growth
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DOI：
10.1016/j.cellimm.2006.06.002
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发表时间：
2006-03-01
影响因子：
4.3
通讯作者：
Sugino, Hiromu
中科院分区：
文献类型：
--
作者：
Funaba, Masayuki;Nakaya, Kohei;Sugino, Hiromu
研究了TGF-β家族参与骨髓源性肥大细胞（BMMC）细胞生长的情况，BMMC在含有商陆促分裂原刺激的脾细胞条件培养基（PWM-SCM）的培养基中培养。Smad 3基因敲除小鼠骨髓基质细胞倍增时间较野生型（WT）小鼠长，且随培养时间延长，差异有增大的趋势。与结果一致，[3-（4，5-二甲基噻唑-2-基）-5-（3-羧基甲氧基苯基）-2-（4-磺基苯基）-2H-四唑鎓，内盐; NITS]的摄取和还原在Smad 3缺陷型BMMC中较低。细胞周期分析显示WT BMMC和Smad 3缺陷型BMMC之间没有明显差异，表明Smad 3缺陷型BMMC的倍增时间延长是由于细胞死亡增加。TGF-β和激活素A由PWM-SCM提供，而不是由BMMC自身产生。通过抗TGF-β中和抗体或包括TGF-β和激活素在内的配体的I型受体抑制剂SB 431542阻断TGF-β途径，可抑制WT BMMC中的NITS摄取和减少，而抗激活素A抗体和SB 431542倾向于抑制Smad 3缺陷型BMMC中的NITS摄取和减少。目前的结果表明，TGF-β诱导和Smad 3介导的信号传导是必不可少的肥大细胞中的最大细胞生长，激活素途径可能是必需的，当肥大细胞的上下文调制Smad 3耗尽。(c)2006年爱思唯尔公司All rights reserved.
The involvement of the TGF-beta 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; NITS] 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-beta and activin A were supplied by PWM-SCM rather than by self-production by BMMC. Blocking the TGF-beta pathway by anti-TGF-beta neutralizing antibody or an inhibitor for the type I receptors for ligands including TGF-beta and activin, SB431542, inhibited NITS 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-beta-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. (c) 2006 Elsevier Inc. All rights reserved.