首页> 外文期刊>American Journal of Physiology >Cyclic mechanical stretch inhibits cell proliferation and induces apoptosis in fetal rat lung fibroblasts.
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Cyclic mechanical stretch inhibits cell proliferation and induces apoptosis in fetal rat lung fibroblasts.

机译:循环机械拉伸抑制胎鼠肺成纤维细胞的细胞增殖并诱导细胞凋亡。

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Development of the pulmonary air sacs is crucial for extrauterine survival. Late fetal lung development is characterized by a thinning of the mesenchyme, which brings pneumocytes and endothelial cells into apposition. We hypothesized that mechanical stretch, simulating fetal breathing movements, plays an important role in this remodeling process. Using a Flexercell Strain Unit, we analyzed the effects of intermittent stretch on cell proliferation and apoptosis activation in fibroblasts isolated from fetal rat lungs during late development. On day 19, intermittent stretch increased cells in G(0)/G(1) by 22% (P = 0.001) and decreased in S phase by 50% (P = 0.003) compared with unstretched controls. Cell proliferation analyzed by 5-bromo-2'-deoxyuridine incorporation showed a similar magnitude of cell cycle arrest (P = 0.04). At this same gestational age, stretch induced apoptosis by two- to threefold over controls, assayed by DNA flow cytometry, terminal deoxynucleotidyl transferase-mediated dUTP-FITC nick-end labeling, and caspase-3 activation. These results indicate that mechanical stretch of fibroblasts isolated during the canalicular stage inhibits cell cycle progression and activates apoptosis. These findings are cotemporal with the mesenchymal thinning that normally occurs in situ.
机译:肺气囊的发育对于宫外生存至关重要。胎儿肺晚期发育的特征是间充质变薄,使肺细胞和内皮细胞并置。我们假设模拟胎儿呼吸运动的机械拉伸在此重塑过程中起重要作用。使用Flexercell应变单元,我们分析了间歇性拉伸对发育后期从胎鼠肺分离的成纤维细胞中细胞增殖和凋亡激活的影响。在第19天,与未拉伸的对照组相比,间歇性拉伸使G(0)/ G(1)中的细胞增加22%(P = 0.001),而在S期减少50%(P = 0.003)。通过5-溴-2'-脱氧尿苷掺入分析的细胞增殖显示相似程度的细胞周期停滞(P = 0.04)。在相同的胎龄,伸展运动比对照组诱导的细胞凋亡高两倍至三倍,通过DNA流式细胞仪,末端脱氧核苷酸转移酶介导的dUTP-FITC缺口末端标记和caspase-3激活进行检测。这些结果表明,在小管阶段分离的成纤维细胞的机械拉伸抑制细胞周期进程并激活细胞凋亡。这些发现与通常在原位发生的间质变薄同时发生。

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