Activation of canonical wnt pathway promotes differentiation of mouse bone marrow-derived MSCs into type II alveolar epithelial cells, confers resistance to oxidative stress, and promotes their migration to injured lung tissue in vitro
Activation of canonical wnt pathway promotes differentiation of mouse bone marrow-derived MSCs into type II alveolar epithelial cells, confers resistance to oxidative stress, and promotes their migration to injured lung tissue in vitro
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经典wnt通路的激活促进小鼠骨髓来源的间充质干细胞分化为II型肺泡上皮细胞，赋予其对氧化应激的抵抗力，并促进其在体外迁移至受损肺组织
DOI：
10.1002/jcp.24282
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发表时间：
2013-06-01
影响因子：
5.6
通讯作者：
Qiu, Hai-bo
中科院分区：
文献类型：
--
作者：
Liu, Ai-ran;Liu, Le;Qiu, Hai-bo
间充质干细胞（mesenchymal stem cells，MSCs）在体内和体外向II型肺泡上皮细胞（type II alveolar epithelial，AT II）分化，是急性肺损伤（acute lung injury，ALI）后上皮再生和恢复的关键，但其分化机制尚不清楚。在本研究中，我们研究了经典的wnt通路在小鼠骨髓来源的间充质干细胞（mMSCs）分化为AT II细胞的作用。使用改良的共培养系统与小鼠肺上皮-12（MLE-12）细胞和小气道生长培养基（SAGM），以有效地驱动mMSCs分化，我们发现，GSK 3和-catenin在经典的Wnt通路在分化过程中上调。当Wnt 3a或LiCl加入到共培养系统中以激活wnt/β-catenin信号转导时，mMSC中AT II细胞的特异性标志物表面活性蛋白（SP）C、SPB和SPD的水平相应增加。通过加入DKK 1抑制该通路，这些因子的表达在一定程度上被抑制。mMSCs的分化率还取决于它们在炎症组织中积累和存活的能力。我们的研究结果表明，激活wnt/-catenin信号促进mMSCs迁移到ALI小鼠来源的肺组织中的Transwell实验，并改善细胞死亡和Bcl-2/Bax的减少由H2O2诱导，同时导致减少GSK 3和-catenin在mMSCs。这些数据支持了mMSCs分化为AT II细胞的潜在机制，涉及经典的wnt通路激活，这可能对它们在ALI中的应用具有重要意义。J.细胞。228：12701283，2013。(c)2012 Wiley Periodicals，Inc.
The differentiation of mesenchymal stem cells (MSCs) into type II alveolar epithelial (AT II) cells in vivo and in vitro, is critical for reepithelization and recovery in acute lung injury (ALI), but the mechanisms responsible for differentiation are unclear. In the present study, we investigated the role of the canonical wnt pathway in the differentiation of mouse bone marrow-derived MSCs (mMSCs) into AT II cells. Using a modified co-culture system with murine lung epithelial-12 (MLE-12) cells and small airway growth media (SAGM) to efficiently drive mMSCs differentiation, we found that GSK 3 and -catenin in the canonical wnt pathway were up-regulated during differentiation. The levels of surfactant protein (SP) C, SPB, and SPD, the specific markers of AT II cells, correspondingly increased in mMSCs when Wnt3a or LiCl was added to the co-culture system to activate wnt/-catenin signaling. The expression of these factors was depressed to some extent by inhibiting the pathway with the addition of DKK 1. The differentiation rate of mMSCs also depends on their abilities to accumulate and survive in inflammatory tissue. Our results suggested that the activation of wnt/-catenin signaling promoted mMSCs migration towards ALI mouse-derived lung tissue in a Transwell assay, and ameliorated the cell death and the reduction of Bcl-2/Bax induced by H2O2, which simultaneously caused reduced GSK 3 and -catenin in mMSCs. These data supports a potential mechanism for the differentiation of mMSCs into AT II cells involving canonical wnt pathway activation, which may be significant to their application in ALI. J. Cell. Physiol. 228: 12701283, 2013. (c) 2012 Wiley Periodicals, Inc.