Department of Respiratory and Critical Care Medicine, Beijing Key Laboratory of Respiratory and Pulmonary Circulation, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China.
Respir Physiol Neurobiol. 2012 Mar 15;180(2-3):237-46. doi: 10.1016/j.resp.2011.11.011. Epub 2011 Dec 2.
The injury and differentiation of alveolar epithelial type II cells induced by alveolar epithelial deformation play important roles in the pathophysiology of ventilator-induced lung injury and repair of the lung injury, respectively. We developed an in vitro rat model to investigate the effects of deformation amplitude, peak deformation, and minimum deformation on the viability and differentiation of type II cells. Rat primary alveolar epithelial type II cells were exposed to a variety of equibiaxial cyclic stretch protocols, and deformation-induced cell survival and differentiation were analyzed. Cell death increased when deformation consisted of change in cell surface area (ΔSA) of 0-37%, 0-50%, 12-50%, 37-50% (P=0.001, P<0.001, P<0.001, and P=0.003, respectively). When ΔSA was at 12-37% and 12-50%, mRNA transcription (P=0.034 and P=0.036) and protein expressions (P=0.008 and P=0.001) of caveolin-1 (a marker for the type I phenotype) increased, in contrast to the decrease of their mRNA transcription of surfactant protein C (a marker for the type II phenotype) (P=0.011, 0.002). These results suggest that amplitude or minimum deformation ≥ 37% ΔSA is an important cause of cell death, and amplitude ≥ 25% ΔSA promotes cell differentiation. Appropriate amplitude (25% ΔSA) can not only avoid cell death but also promote cell differentiation.
肺泡上皮细胞变形引起的肺泡上皮细胞 II 型损伤和分化分别在呼吸机诱导性肺损伤的病理生理学和肺损伤修复中起重要作用。我们建立了一种体外大鼠模型，以研究变形幅度、变形峰值和最小变形对 II 型细胞活力和分化的影响。将大鼠原代肺泡上皮细胞 II 型暴露于各种等张循环拉伸方案中，并分析变形诱导的细胞存活和分化。当变形由细胞表面积变化（ΔSA）为 0-37%、0-50%、12-50%和 37-50%组成时，细胞死亡增加（P=0.001、P<0.001、P<0.001 和 P=0.003）。当 ΔSA 在 12-37%和 12-50%时，小窝蛋白-1（I 型表型的标志物）的 mRNA 转录（P=0.034 和 P=0.036）和蛋白表达（P=0.008 和 P=0.001）增加，而表面活性蛋白 C（II 型表型的标志物）的 mRNA 转录则减少（P=0.011、0.002）。这些结果表明，幅度或最小变形≥37%ΔSA 是细胞死亡的重要原因，幅度≥25%ΔSA 促进细胞分化。适当的幅度（25%ΔSA）不仅可以避免细胞死亡，还可以促进细胞分化。
