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过表达的趋化因子CXCL12通过PI3K/Akt途径促进骨髓基质干细胞Connexins的表达

CXCL12 Chemokine Up-regulates Connexins Expression in Mesenchymal Stem Cells Through PI3K/Akt Pathway
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摘要 研究过表达的趋化因子CXCL12是否通过PI3K/Akt信号途径促进了骨髓基质干细胞膜上缝隙连接蛋白Connexin40、Connexin43和Connexin45的表达。采用重组DNA技术使骨髓基质干细胞过表达趋化因子CXCL12,采用Western blot法测定趋化因子CXCL12过表达后骨髓基质干细胞Connexin40、Connexin43、Connexin45、Akt、pAkt表达的变化情况,并用CXCL12受体和Akt途径阻断剂明确CXCL12和PI3K/Akt途径在这一过程中的作用。基因重组后骨髓干细胞过表达了趋化因子CXCL12,CXCL12过表达使骨髓基质干细胞膜上Connexin40、Connexin43和Connexin45表达明显增多,且CXCL12的这一作用是通过PI3K/Akt这一途径实现的。趋化因子CXCL12通过PI3K/Akt途径使骨髓基质干细胞膜上Connexin40、Connexin43和Connexin45的表达增加,可促进移植后干细胞与宿主心肌细胞形成有效的电耦合,从而有利于移植后干细胞的存活并发挥治疗作用。 Heart cell therapy provides an unconvention connective measure to compensate for myocyte loss in the infacted heart.Nevertheless poor survival of doner cells is one of the major concerns that hampers a better prognosis.Additionally,poor engraftment and lack of functional coupling of donor cells with the viable host tissue greatly impede cell-to-cell signaling and electric conmmunication.Connexins with its dual role as an antiapoptotic and as a gap-junctional protein,can effectively resolve both of these issues.CXCL12,a member of the chemokine CXC subfamily,may play a role in stem cell survival and proliferation.CXCL12 activates several signaling pathways in stem cells,particularly the survival kinase PI3K/Akt which is also an important mediator of Cx-43 expression.On the basis of these characteristics of CXCL12 and Akt,the potential of overexpressed CXCL12 to improve Cx43 expression via PI3K/Akt pathway was investigated.Mesenchymal stem cells were transfected with adenovirus for increasing CXCL12 secretion.Connexin40,Connexin43,Connexin45 and Akt enzyme were evaluted by Western blot analysis.Transfection CXCL12 resulted increased CXCL12 in situ.Increased CXCL12 induced elevated Connexin40,Connexin43 and Connexin45 expression,which was established by activated PI3K/Akt pathway.Increased CXCL12 leads to enhanced expression of Connexin40,Connexin43 and Connexin45 through PI3K/Akt pathway,which may augment mesenchymal stem cell survival and integration in the infracted heart.
出处 《中国生物工程杂志》 CAS CSCD 北大核心 2012年第4期18-21,共4页 China Biotechnology
关键词 骨髓基质干细胞 CXCL12 CONNEXIN43 细胞移植 Mesenchymal stem cells CXCL12 chemokine Connexin43 Cell transplantation
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参考文献12

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