Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Stem Cells Dev. 2013 Jan 15;22(2):239-47. doi: 10.1089/scd.2012.0192. Epub 2012 Oct 5.
Resistin-like molecule α (RELMα) is highly upregulated in the lungs of mice subjected to hypoxia. It is secreted from pulmonary epithelium and causes potent mitogenic, angiogenic, and vasoconstrictive effects in the lung vasculature. By using bone marrow transplantation in mice, we previously showed that RELMα is able to increase the number of bone marrow-derived cells in lung tissue, especially in the remodeling pulmonary vasculature. The current study investigated the effect of RELMα on progenitor stem cell content in mouse lung. Hypoxia, while stimulating RELMα expression, caused an increase in the number of Sca1(+)/CD45(-) progenitor cells in lungs of wild-type mice, but not in lungs of RELMα knockout mice. An in vitro study with cultured mesenchymal stem cells (MSCs) showed that RELMα induced a robust proliferative response that was dependent on Phosphatidylinositol 3-kinase/Akt and Erk activation. RELMα treatment of MSCs caused upregulation of a large number of genes involved in cell cycle, mitosis, organelle, and cytoskeleton biogenesis, and DNA metabolism. MSCs cultured in RELMα-supplemented media were able to maintain their differentiation potential into adipogenic, osteogenic, or mesenchymal phenotypes, although adipogenic differentiation was partially inhibited. These results demonstrate that RELMα may be involved in stem cell proliferation in the lung, without affecting differentiation potential.
抵抗素样分子 α（RELMα）在缺氧小鼠的肺部高度上调。它由肺上皮细胞分泌，在肺血管中引起强烈的有丝分裂、血管生成和血管收缩作用。通过在小鼠中进行骨髓移植，我们之前表明 RELMα 能够增加肺组织中骨髓来源细胞的数量，特别是在重塑的肺血管中。本研究探讨了 RELMα 对小鼠肺祖细胞含量的影响。缺氧刺激 RELMα 表达的同时，导致野生型小鼠肺部 Sca1(+)/CD45(-)祖细胞数量增加，但 RELMα 敲除小鼠肺部则没有。体外培养间充质干细胞（MSCs）的研究表明，RELMα 诱导了强烈的增殖反应，该反应依赖于磷脂酰肌醇 3-激酶/ Akt 和 Erk 的激活。RELMα 处理 MSCs 导致大量参与细胞周期、有丝分裂、细胞器和细胞骨架生物发生以及 DNA 代谢的基因上调。在补充 RELMα 的培养基中培养的 MSCs 能够保持其向脂肪生成、成骨或间充质表型分化的潜力，尽管脂肪生成分化部分受到抑制。这些结果表明，RELMα 可能参与肺中的干细胞增殖，而不影响分化潜力。
