Sdf-1 (CXCL12) induces CD9 expression in stem cells engaged in muscle regeneration.
Sdf-1 (CXCL12) induces CD9 expression in stem cells engaged in muscle regeneration.
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DOI：
10.1186/s13287-015-0041-1
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发表时间：
2015-03-24
影响因子：
7.5
通讯作者：
Ciemerych MA
中科院分区：
文献类型：
--
作者：
Brzoska E;Kowalski K;Markowska-Zagrajek A;Kowalewska M;Archacki R;Plaskota I;Stremińska W;Jańczyk-Ilach K;Ciemerych MA
了解干细胞动员到受伤的骨骼肌的机制是肌肉疾病治疗发展的先决条件。目前研究的许多干细胞类型都具有生肌潜力;然而，当引入血流或直接引入组织时，它们不能有效地移植受伤的肌肉。因此，它们在治疗中的应用仍然有限。以前，我们已经表明，基质衍生因子-1（Sdf-1）引起动员内源性（非移植）干细胞进入受损骨骼肌，改善再生。在这里，我们证明了Sdf-1的有益作用依赖于干细胞中四跨膜蛋白CD 9表达的上调。在大鼠骨骼肌和小鼠Pax 7-/-骨骼肌再生过程中，分析了Sdf-1处理后粘附蛋白（包括CD 9）的表达模式，其特征在于卫星细胞数量减少。接下来，我们研究了卫星细胞来源的成肌细胞、骨髓来源的间充质干细胞和胚胎干细胞在Sdf-1处理或沉默CXCR 4和CXCR 7表达后CD 9水平的变化。最后，我们研究了Sdf-1处理后干细胞与成肌细胞融合的潜力。Pax 7-/-小鼠的体内分析强烈表明，Sdf-1-介导的CD 9水平的增加，也在动员的干细胞。在不存在CXCR 4受体的情况下，Sdf-1对CD 9表达的作用被阻断。接下来，体外研究表明，Sdf-1不仅在卫星细胞来源的成肌细胞中，而且在骨髓来源的间充质干细胞以及胚胎干细胞中增加CD 9的水平。重要的是，Sdf-1处理的细胞更有效地迁移并与成肌细胞融合。我们认为Sdf-1结合CXCR 4受体通过上调CD 9的表达来改善骨骼肌再生，从而影响干细胞向受损肌肉的动员。
Understanding the mechanism of stem cell mobilization into injured skeletal muscles is a prerequisite step for the development of muscle disease therapies. Many of the currently studied stem cell types present myogenic potential; however, when introduced either into the blood stream or directly into the tissue, they are not able to efficiently engraft injured muscle. For this reason their use in therapy is still limited. Previously, we have shown that stromal-derived factor-1 (Sdf-1) caused the mobilization of endogenous (not transplanted) stem cells into injured skeletal muscle improving regeneration. Here, we demonstrate that the beneficial effect of Sdf-1 relies on the upregulation of the tetraspanin CD9 expression in stem cells. The expression pattern of adhesion proteins, including CD9, was analysed after Sdf-1 treatment during regeneration of rat skeletal muscles and mouse Pax7-/- skeletal muscles, that are characterized by the decreased number of satellite cells. Next, we examined the changes in CD9 level in satellite cells-derived myoblasts, bone marrow-derived mesenchymal stem cells, and embryonic stem cells after Sdf-1 treatment or silencing expression of CXCR4 and CXCR7. Finally, we examined the potential of stem cells to fuse with myoblasts after Sdf-1 treatment. In vivo analyses of Pax7-/- mice strongly suggest that Sdf-1-mediates increase in CD9 levels also in mobilized stem cells. In the absence of CXCR4 receptor the effect of Sdf-1 on CD9 expression is blocked. Next, in vitro studies show that Sdf-1 increases the level of CD9 not only in satellite cell-derived myoblasts but also in bone marrow derived mesenchymal stem cells, as well as embryonic stem cells. Importantly, the Sdf-1 treated cells migrate and fuse with myoblasts more effectively. We suggest that Sdf-1 binding CXCR4 receptor improves skeletal muscle regeneration by upregulating expression of CD9 and thus, impacting at stem cells mobilization to the injured muscles.
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影响因子：
7.8
作者：
Asakura, Atsushi;Seale, Patrick;Girgis-Gabardo, Adele;Rudnicki, Michael A
通讯作者：
Rudnicki, Michael A
影响因子：
23.9
作者：
Benchaouir, Rachid;Meregalli, Mirella;Torrente, Yvan
通讯作者：
Torrente, Yvan
影响因子：
21.3
作者：
Dellavalle, Arianna;Sampaolesi, Maurilio;Cossu, Giulio
通讯作者：
Cossu, Giulio
影响因子：
3.9
作者：
Grabowska, Iwona;Szeliga, Anna;Brzoska, Edyta
通讯作者：
Brzoska, Edyta
影响因子：
4
作者：
Archacka, Karolina;Denkis, Agnieszka;Moraczewski, Jerzy
通讯作者：
Moraczewski, Jerzy