Interleukin-27 induces the endothelial differentiation in Sca-1+ cardiac resident stem cells.
Interleukin-27 induces the endothelial differentiation in Sca-1+ cardiac resident stem cells.
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DOI：
10.1016/j.cyto.2015.06.009
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发表时间：
2015-10
期刊：
影响因子：
3.8
通讯作者：
Tomohiro Tanaka;Masanori Obana;T. Mohri;Masaki Ebara;Y. Otani;Makiko Maeda;Y. Fujio
中科院分区：
文献类型：
--
作者：
Tomohiro Tanaka;Masanori Obana;T. Mohri;Masaki Ebara;Y. Otani;Makiko Maeda;Y. Fujio
细胞因子在心脏修复和再生中起重要作用。最近，我们发现白细胞介素（IL）-6家族细胞因子通过STAT 3/Pim-1信号通路诱导Sca-1+心脏干细胞向内皮细胞分化。相比之下，IL-12家族细胞因子在心脏中的生物学功能仍有待阐明，尽管它们与IL-6显示出结构同源性。在本研究中，我们研究了IL-12家族细胞因子对心脏Sca-1+细胞转分化为心脏细胞的影响。RT-PCR结果显示，心肌Sca-1+细胞表达IL-27受体α（IL-27 R α），而不表达IL-12 R和IL-23 R。在心脏损伤模型中，小鼠心脏中IL-27的转录表达升高。有趣的是，IL-27刺激14天诱导了内皮细胞（EC）标记基因，如CD-31和VE-钙粘蛋白。免疫印迹分析阐明IL-27处理快速磷酸化STAT 3。IL-27上调Pim-1的表达，但显性负性STAT 3的过表达废除了IL-27对Pim-1的诱导。最后，腺病毒转染显性阴性Pim-1抑制IL-27诱导的心脏Sca-1+细胞EC分化。这些发现表明，IL-27促进了心脏干细胞向EC谱系的定向分化，可能导致新血管形成作为一种新的生物学功能。IL-27不仅可以调节炎症反应，还可以通过炎症部位的干细胞分化来维持组织的稳态。
Cytokines play important roles in cardiac repair and regeneration. Recently, we demonstrated that interleukin (IL)-6 family cytokines induce the endothelial differentiation of Sca-1+ cardiac resident stem cells through STAT3/Pim-1 signaling pathway. In contrast, the biological functions of IL-12 family cytokines in heart remain to be elucidated, though they show structural homology with IL-6. In the present study, we examined the effects of IL-12 family cytokines on the transdifferentiation of cardiac Sca-1+ cells into cardiac cells. RT-PCR analyses revealed that IL-27 receptor α (IL-27Rα), but not IL-12R or IL-23R, was expressed in cardiac Sca-1+ cells. The transcript expression of IL-27 was elevated in murine hearts in cardiac injury models. Intriguingly, IL-27 stimulation for 14 days induced the endothelial cell (EC) marker genes, such asCD-31andVE-cadherin. Immunoblot analyses clarified that IL-27 treatment rapidly phosphorylated STAT3. IL-27 upregulated the expression of Pim-1, but the overexpression of dominant negative STAT3 abrogated the induction of Pim-1 by IL-27. Finally, adenoviral transfection of dominant negative Pim-1 inhibited IL-27-induced EC differentiation of cardiac Sca-1+ cells. These findings demonstrated that IL-27 promoted the commitment of cardiac stem cells into the EC lineage, possibly leading to neovascularization as a novel biological function. IL-27 could not only regulate the inflammation but also contribute to the maintenance of the tissue homeostasis through stem cell differentiation at inflammatory sites.