Hyperoxia inhibits proliferation of Mv1Lu epithelial cells independent of TGF-beta signaling.
Hyperoxia inhibits proliferation of Mv1Lu epithelial cells independent of TGF-beta signaling.
复制标题
高氧抑制 Mv1Lu 上皮细胞的增殖，不依赖于 TGF-β 信号传导。
DOI：
10.1152/ajplung.1999.277.6.l1172
复制
发表时间：
1999
期刊：
影响因子：
--
通讯作者：
O'Reilly,MA
中科院分区：
文献类型：
--
作者：
Rancourt,RC;Staversky,RJ;Keng,PC;O'Reilly,MA
高浓度的O2抑制上皮细胞增殖，恢复在室内空气中。为了确定生长停滞是否由转化生长因子-β（TGF-β）介导，在貂肺上皮细胞系Mv1Lu和I型TGF-β受体缺陷的克隆变体R1B中评估了暴露于高氧期间细胞增殖的变化。碘化丙啶染色显示TGF-β处理的Mv1Lu细胞在细胞周期的G1期聚集，而R1B细胞的增殖不受TGF-β的影响。与此相反，高氧抑制增殖的两个细胞系在24小时内曝光通过积累在S期。TGF-β处理并暴露于高氧的Mv1Lu细胞在G1期积累，表明TGF-β可以抑制单独高氧观察到的S期积累。细胞周期蛋白A在暴露于室内空气或高氧的细胞中被检测到，而在TGF-β阻滞于G1期的细胞中细胞生长减少。最后，高氧不能激活Mv1Lu和R1B细胞中的TGF-β依赖性转录报告基因。这些发现揭示了高氧引起的简单生长停滞涉及S期进展的缺陷，其独立于TGF-β信号传导。
High concentrations of O2inhibit epithelial cell proliferation that resumes on recovery in room air. To determine whether growth arrest is mediated by transforming growth factor-β (TGF-β), changes in cell proliferation during exposure to hyperoxia were assessed in the mink lung epithelial cell line Mv1Lu and the clonal variant R1B, which is deficient for the type I TGF-β receptor. Mv1Lu cells treated with TGF-β accumulated in the G1phase of the cell cycle as determined by propidium iodide staining, whereas proliferation of R1B cells was unaffected by TGF-β. In contrast, hyperoxia inhibited proliferation of both cell lines within 24 h of exposure through an accumulation in the S phase. Mv1Lu cells treated with TGF-β and exposed to hyperoxia accumulated in the G1phase, suggesting that TGF-β can inhibit the S phase accumulation observed with hyperoxia alone. Cyclin A was detected in cultures exposed to room air or growth arrested by hyperoxia while decreasing in cells growth arrested in the G1phase by TGF-β. Finally, hyperoxia failed to activate a TGF-β-dependent transcriptional reporter in both Mv1Lu and R1B cells. These findings reveal that simple growth arrest by hyperoxia involves a defect in S phase progression that is independent of TGF-β signaling.