Effect of Hypoxia on the Differentiation and the Self-Renewal of Metanephrogenic Mesenchymal Stem Cells.
Effect of Hypoxia on the Differentiation and the Self-Renewal of Metanephrogenic Mesenchymal Stem Cells.
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缺氧对后肾间充质干细胞分化和自我更新的影响
DOI：
10.1155/2017/7168687
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发表时间：
2017
影响因子：
4.3
通讯作者：
Teng J
中科院分区：
文献类型：
--
作者：
Liu S;Song N;He J;Yu X;Guo J;Jiao X;Ding X;Teng J
低氧是发育过程中一个重要的影响因素。胚胎肾脏在整个发育过程中都暴露在低氧环境中。Wnt/β-Catenin通路在后肾源性间充质干细胞的分化和自我更新过程中起重要作用。因此，我们推测低氧可能通过Wnt/β-Catenin途径调节MMSCs的分化和多能性。为了验证这一假设，将胚胎18.5天的大鼠的MMSCs分别在常氧(21%O2)和低氧(1%O2)条件下培养。检测低氧对体外培养的骨髓间充质干细胞的分化、干化、增殖、凋亡及Wnt/β-Catenin通路活性的影响。结果表明，低氧条件下肾小管上皮细胞(E-钙粘蛋白+或CK18+)数量增加，肾小管上皮细胞标志物CDH6、AQP1和OPN表达增加，干细胞数量和增殖减少(Six-2+或CITED1+)，并诱导细胞凋亡。此外，低氧还降低了WNT4及其下游分子β-连环蛋白、LeF-1和Axin2的表达。LiC l或Bio激活Wnt/β-catenin通路可改变低氧对骨髓间充质干细胞分化和自我更新的影响。因此，我们得出结论，低氧通过抑制Wnt/β-Catenin途径诱导MMSCs分化并抑制其自我更新。这些观察进一步加深了我们对低氧对肾脏影响的理解。
Hypoxia is an important and influential factor in development. The embryonic kidney is exposed to a hypoxic environment throughout its development. The Wnt/β-catenin pathway plays vital roles in the differentiation and self-renewal of metanephrogenic mesenchymal stem cells (MMSCs) from which the kidney is derived. Thus, we hypothesized that hypoxia can regulate the differentiation and pluripotency of MMSCs through the Wnt/β-catenin pathway. To test this hypothesis, MMSCs from rats at embryonic day 18.5 were cultured in normoxic (21% O2) and hypoxic (1% O2) conditions. The effects of hypoxia on differentiation, stemness, proliferation, and apoptosis of cultured MMSCs and on the activity of the Wnt/β-catenin pathway were tested. Our results revealed that the hypoxic condition increased the number of epithelial cells (E-cadherin+ or CK18+) as well the expression of markers of renal tubule epithelia cells (CDH6, Aqp1, and OPN), decreased the number and proliferation of stem cells (SIX-2+ or CITED1+), and induced apoptosis. Additionally, hypoxia reduced the expression of Wnt4 as well as its downstream molecules β-catenin, LEF-1, and Axin2. Activation of the Wnt/β-catenin pathway by LiCl or BIO modified the effects of hypoxia on the differentiation and self-renewal of MMSCs. Thus, we concluded that hypoxia induces the differentiation and inhibits the self-renewal of MMSCs by inhibiting the Wnt/β-catenin pathway. The observations further our understanding of the effects of hypoxia on kidney.