The cellular kinetics of lung alveolar epithelial cells and its relationship with lung tissue repair after acute lung injury.

The cellular kinetics of lung alveolar epithelial cells and its relationship with lung tissue repair after acute lung injury.
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急性肺损伤后肺泡上皮细胞的细胞动力学及其与肺组织修复的关系

DOI:
10.1186/s12931-016-0480-y
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发表时间:
2016-12-07
影响因子:
5.8
通讯作者:
Jiang JX
Jiang JX
中科院分区:
医学2区
文献类型:
--
作者:
Zeng L;Yang XT;Li HS;Li Y;Yang C;Gu W;Zhou YH;Du J;Wang HY;Sun JH;Wen DL;Jiang JX

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哺乳动物的器官再生被假设需要一个功能性的干细胞或祖细胞库,但这些细胞在肺再生中的作用尚不清楚。基于肺泡上皮细胞是肺泡组织再生的主要细胞,我们建立了失血性休克和脂多糖(LPS)肺损伤模型。利用该模型,我们分析了肺泡上皮细胞的细胞动力学。结果表明,肺泡上皮2型细胞(AEC 2s)在急性肺损伤中具有抗损伤能力,可能是参与肺损伤和修复的主要细胞。观察大鼠急性肺损伤后肺组织HGF、c-Met的表达与AEC 2s增殖的关系。当分离的原代AEC 2s与c-Met抑制剂SU 11274共培养时,AEC 2s的增殖受到抑制。另外,在ALI大鼠体内给予SU 11274后,AEC 2的数量显著减少。进一步证明HGF/c-Met信号通路在ALI诱导的AEC 2s增殖中起重要作用。AEC 2在急性肺损伤中具有抗损伤性,HGF/c-Met信号通路在ALI后AEC 2的增殖中至关重要。
Organ regeneration in mammals is hypothesized to require a functional pool of stem or progenitor cells, but the role of these cells in lung regeneration is unknown. Based on the fact that postnatal regeneration of alveolar tissue has been attributed to alveolar epithelial cells, we established a hemorrhagic shock and Lipopolysaccharide (LPS) lung injury model. Using this model, we analyzed the cellular kinetics of lung alveolar epithelial cells. The results showed that alveolar epithelium type 2 cells (AEC2s) are damage resistant during acute lung injury, they might be the main cells involved in lung injury and repair. Then we observed the relationship between the expression of HGF, c-Met following ALI in rat lung and proliferation of AEC2s. The proliferation of AEC2s was inhibited when isolated primary AEC2s were co-cultured with c-Met inhibitor SU11274. Furthermore, the numbers of AEC2s was significantly decreased when ALI rats were administrated with SU11274 in vivo. It provided further evidence that the HGF/c-Met signaling plays a vital role in ALI-induced AEC2s proliferation. AEC2s are damage resistant during acute lung injury and the HGF/c-Met signaling pathway is of vital importance in the proliferation of AEC2s after ALI.
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