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CXCL12 Chemokine Up-regulates Connexins Expression in Mesenchymal Stem Cells Through PI3K/Akt Pathway |
CHI Xiao-wei, HOU Jing-bo, MENG Jia, ZHANG Yi-na |
The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China |
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Abstract 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.
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Received: 27 June 2011
Published: 25 April 2012
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[1] Johnstone S R,Best A K,Wright C S,et al. Enhanced connexin 43 expression delays intra-mitoitc duration and cell cycle traverse independently of gap junction channel function.J Cell Biochem,2010,110(3): 772-782.
[2] Rottlaneder D,Bonegler K,Wolny M,et al. Connexin 43 acts as a cytoprotective mediator of signal transduction by stimulating mitochondrial KATP channels in mouse cardiomyocytes. J Clin Invest, 2010,120(5):1441-1453.
[3] Celeste M N,Christopher S.Cell-cell signaling by direct contact increases cell proliferation via a PI3K-dependent signal.FEBS Let,2002,514:238-242.
[4] Song H,Hwang H J,Chang W,et al. Cardiomyocytes from phorbol myristate acetateactivated mesenchymal stem cells restore electromechanical function in infarcted rat hearts.PNAS,2011,108(1):296-301.
[5] Mcspadden L C,Kirkton R D,Bursac N.Electronic loading of anisotropic cardiac monolayers by unexcitable cells depends on connexin type and expression level.Am J Physiol Cell Physiol,2009,297:339-351.
[6] Dawn M P,Rebecca Y K,Nima B,et al.Structrual coupling of cardiomyocytes and noncardiomyocytes:quantitative comparisons using a novel micropatterned cell pair assay. Am J Physiol Heart Circ Physiol,2008,295:390-400.
[7] Zhang M,Mal N,Kiedrowski M,et al. SDF-1 expression by mesenchymal stem cells results in trophic support of cardiac myocytes after myocardial infarction. FASEB J,2007,21: 3197-3207.
[8] Pasha Z,Wang Y G,Sheikh R,et al.Precinditioning enhances cell survival and differentiation of stem cells during transplantation in infracted myocardium.Cardiovas Res,2008,77:134-142.
[9] Saxena A,Fish J E,White M D,et al.Stromal cell-derived factor-1 is cardioprotective after myocardial infarction.Circulation,2008,117: 2224-2231.
[10] Xia X, Batra N, Shi Q,et al. Prostaglandin promotion of osteocyte gap junction function through transcriptional regulation of connexin 43 by glycogen synthase kinase 3/beta-catenin signaling. Mol Cell Biol,2010, 30(1):206-219.
[11] Lu G, Haider H K, Jiang S,et al.Sca-1+ stem cell survival and engraftment in the infarcted heart: dual role for preconditioning-induced connexin43.Circulation,2009,119(19): 2587-2596.
[12] Bhattacharjee R, Kaneda M, Nakahama K,et al. The steady-state expression of connexin43 is maintained by the PI3K/Akt in osteoblasts. Biochem Biophys Res Commun,2009,382(2):440-444.
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