Activation of Type II Cells into Regenerative Stem Cell Antigen-1+ Cells during Alveolar Repair
Activation of Type II Cells into Regenerative Stem Cell Antigen-1+ Cells during Alveolar Repair
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DOI：
10.1165/rcmb.2013-0497oc
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发表时间：
2015-07-01
影响因子：
6.4
通讯作者：
Malik, Asrar B.
中科院分区：
文献类型：
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作者：
Liu, Yuru;Kumar, Varsha Suresh;Malik, Asrar B.
肺泡上皮由两种细胞类型组成：I型细胞占气体交换表面积的95%，而II型细胞分泌表面活性剂，同时保留转化为I型细胞以诱导肺泡修复的能力。在铜绿假单胞菌诱导的肺损伤小鼠模型中使用谱系追踪分析，我们鉴定了一群干细胞抗原（Sca）-1表达的II型细胞，其具有介导肺泡修复的祖细胞特性。这些细胞被证明是不同于以前报道的Sca-1表达支气管肺泡干细胞。基因芯片和Wnt报告基因研究表明，Sp-C（+）Sca-1（+）细胞表达Wnt信号通路基因，抑制Wnt/beta-catenin信号通路可抑制Sp-C（+）Sca-1（+）细胞的体外再生功能。因此，铜绿假单胞菌介导的肺损伤诱导了II型细胞Sca-1（+）亚群的产生。介导肺泡上皮修复的Sp-C（+）Sca-1（+）细胞的祖细胞表型可能涉及Wnt信号。
The alveolar epithelium is composed of two cell types: type I cells comprise 95% of the gas exchange surface area, whereas type II cells secrete surfactant, while retaining the ability to convert into type I cells to induce alveolar repair. Using lineage-tracing analyses in the mouse model of Pseudomonas aeruginosa-induced lung injury, we identified a population of stem cell antigen (Sca)-1-expressing type II cells with progenitor cell properties that mediate alveolar repair. These cells were shown to be distinct from previously reported Sca-1-expressing bronchioalveolar stem cells. Microarray and Wnt reporter studies showed that surfactant protein (Sp)-C(+)Sca-1(+) cells expressed Wnt signaling pathway genes, and inhibiting Wnt/beta-catenin signaling prevented the regenerative function of Sp-C(+)Sca-1(+) cells in vitro. Thus, P. aeruginosa-mediated lung injury induces the generation of a Sca-1(+) subset of type II cells. The progenitor phenotype of the Sp-C(+)Sca-1(+) cells that mediates alveolar epithelial repair might involve Wnt signaling.