Primary and immortalized mouse epicardial cells undergo differentiation in response to TGFβ
Primary and immortalized mouse epicardial cells undergo differentiation in response to TGFβ
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DOI：
10.1002/dvdy.21421
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发表时间：
2008-02-01
影响因子：
2.5
通讯作者：
Barnett, Joey V.
中科院分区：
文献类型：
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作者：
Austin, Anita F.;Compton, Leigh A.;Barnett, Joey V.
心外膜细胞是冠状血管发育所必需的。转化生长因子β（TGF β）诱导鸡心外膜细胞上皮特征丧失和平滑肌分化。在这里，我们表明，心外膜外植体从胚胎天（E）11.5小鼠胚胎与TGF β 1或TGF β 2孵育失去上皮特性，并进行平滑肌分化。为了进一步研究TGF β信号传导，我们产生了永生化的小鼠心外膜细胞。来自E10.5、11.5和13.5的细胞形成紧密堆积的上皮并表达心外膜标志物Wilm's肿瘤1（WT 1）。TGF β诱导闭合小带-1（ZO-1）的丢失以及与平滑肌分化一致的SM 22 α和钙调蛋白的出现。抑制激活素受体样激酶（ALK）5或p160 rho激酶活性可阻止TGF β的作用，而抑制p38丝裂原活化蛋白（MAP）激酶则不能。这些数据表明，TGF β诱导心外膜细胞分化，并且永生化心外膜细胞提供了合适的分化模型。
Cells derived from the epicardium are required for coronary vessel development. Transforming growth factor beta (TGF beta) induces loss of epithelial character and smooth muscle differentiation in chick epicardial cells. Here, we show that epicardial explants from embryonic day (E) 11.5 mouse embryos incubated with TGF beta 1 or TGF beta 2 lose epithelial character and undergo smooth muscle differentiation. To further study TGF beta Signaling, we generated immortalized mouse epicardial cells. Cells from E10.5,11.5, and 13.5 formed tightly packed epithelium and expressed the epicardial marker Wilm's tumor 1 (WT1). TGF beta induced the loss of zonula occludens-1 (ZO-1) and the appearance of SM22 alpha and calponin consistent with smooth muscle differentiation. Inhibition of activin receptor-like kinase (ALK) 5 or p160 rho kinase activity prevented the effects of TGF beta while inhibition of p38 mitogen activated protein (MAP) kinase did not. These data demonstrate that TGF beta induces epicardial cell differentiation and that immortalized epicardial cells provide a suitable model for differentiation.