Analysis of the cytoprotective effect of STAT3 on pulmonary epithelial cell injury

目的首次发现介导白细胞介素-6 （IL-6）作用的信号分子vestat3。最近的研究表明，它具有细胞保护作用。然而，尚不清楚它是否也对肺上皮细胞具有细胞保护作用。这个研究项目是为了澄清这个问题。IL-6对过氧化氢应激诱导的肺上皮细胞A549死亡具有剂量依赖性的细胞保护作用。这种作用是通过STAT3激活介导的。我们使用肺上皮细胞中STAT3表达完全缺失的肺特异性STAT3敲除小鼠进行高氧实验。这些基因敲除小鼠的存活率低于野生型小鼠。组织学研究显示，在这些基因敲除小鼠中，肺上皮细胞死亡明显。采用肺特异性STAT3敲除小鼠进行博来霉素实验。这些基因敲除小鼠的肺部纤维化变化比野生型小鼠更严重。这些基因敲除小鼠的存活率也有所下降。肺上皮细胞凋亡参与了敲除小鼠肺纤维化的机制。结论：这些发现表明STAT3对多种应激诱导的肺上皮细胞损伤具有细胞保护作用。这一结果表明，激活肺上皮细胞中的STAT3可能是肺损伤（如肺纤维化）的一种治疗策略。

ObjectiveSTAT3 was first discovered as a signal molecule which mediated the effects of Interleukin-6 (IL-6). Recent studies have revealed that it has a cytoprotective effect. However, it remains still unclear whether it is also cytoprotecitve for pulmonary epithelial cells. This research project has been done to clarify this questionResults.1. IL-6 has a cytoprotective effect onpulmonary epithelial cell A549 death induced by hydrogen peroxide stress in a dose dependent manner. This effect is mediated via STAT3 activation2 Lung specific STAT3 knockout mice in which STAT3 expression in pulmonary epithelial cell is exclusively deficient was used for hyperoxia experiments. The survival rate of these knockout mice was low tempered with that of wild type mice. Histological studies revealed that pulmonary epithelial cell death was prominent in these knockout mice.3. Lung specific STAT3 knockout mice was used for bleomycin experiments. Fibrotic changes were more severe in the lungs of these knockout mice tempered to those of wild type mice. Survival rate was also decreased in these knockout mice. Apoptosis of Pulmonary epithelial cells was involved in the mechanisms of the prominent pulmonary fibrosis in these knockout mice.Conclusions.These findings demonstrate that STAT3 has a cytoprotective effect on pulmonary epithelial cell injury induced by several stress. This result suggests that STAT3 activation in the pulmonary epithelial cells could be a therapeutic strategy for lung injury such as pulmonary fibrosis.