CXCR4 活性突变体的转基因表达研究。对造血干/祖细胞归巢和植入效率的上调具有潜在前景。
Transgene expression study of CXCR4 active mutants. Potential prospects in up-modulation of homing and engraftment efficiency of hematopoietic stem/progenitor cells.
机构信息
a Stem Cell & Gene Therapy Research Group ; Institute of Nuclear Medicine & Allied Sciences ; Delhi , India.
出版信息
Cell Adh Migr. 2014;8(4):384-8. doi: 10.4161/cam.29285.
Abstract
Homing and engraftment, a determining factor in hematopoietic stem cell transplantation success is defined as a process through which hematopoietic stem/progenitor cells (HSPCs) lodge recipient bone marrow. SDF-1/CXCR4 axis acts as a principle regulator in homing and engraftment, however, CXCR4 signaling is dependent upon expression of CXCR4 and its ligand SDF-1, which is highly dynamic. Hence, present investigation was aimed to explore the potential of CXCR4 constitutive active mutants (CXCR4-CAMs) in overcoming the limitation of CXCR4 signaling and up-modulate its efficiency in homing and engraftment. Regulated transgene expression study of these mutants revealed their significantly enhanced cell adhesion efficiency to endothelium and extracellular matrix protein. This altogether indicates promising prospects of CXCR4-CAMs in research aimed to improve HSPCs engraftment efficiency.
摘要
归巢和植入是造血干细胞移植成功的决定因素，它被定义为造血干/祖细胞（HSPCs）定居受体骨髓的过程。SDF-1/CXCR4 轴作为归巢和植入的主要调节剂，然而，CXCR4 信号取决于 CXCR4 和其配体 SDF-1 的表达，而 SDF-1 的表达是高度动态的。因此，本研究旨在探索 CXCR4 组成型激活突变体（CXCR4-CAMs）在克服 CXCR4 信号限制并提高其归巢和植入效率方面的潜力。这些突变体的调控转基因表达研究表明，它们与内皮细胞和细胞外基质蛋白的黏附效率显著增强。这一切都表明，CXCR4-CAMs 在旨在提高 HSPC 植入效率的研究中具有广阔的前景。
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1
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J Stem Cells Regen Med. 2013 Apr 30;9(1):19-27. doi: 10.46582/jsrm.0901005. eCollection 2013.
2
Stromal-derived factor-1/CXCR4 signaling: indispensable role in homing and engraftment of hematopoietic stem cells in bone marrow.
Stem Cells Dev. 2011 Jun;20(6):933-46. doi: 10.1089/scd.2010.0263. Epub 2011 Feb 2.
3
Regulation of CXCR4 signaling.
Biochim Biophys Acta. 2007 Apr;1768(4):952-63. doi: 10.1016/j.bbamem.2006.11.002. Epub 2006 Nov 10.
4
Up-regulation of CXCR4 expression in PC-3 cells by stromal-derived factor-1alpha (CXCL12) increases endothelial adhesion and transendothelial migration: role of MEK/ERK signaling pathway-dependent NF-kappaB activation.
Cancer Res. 2005 Nov 1;65(21):9891-8. doi: 10.1158/0008-5472.CAN-05-1293.
5
How do stem cells find their way home?
Blood. 2005 Sep 15;106(6):1901-10. doi: 10.1182/blood-2005-04-1417. Epub 2005 May 12.
6
Overexpression of CXCR4 on human CD34+ progenitors increases their proliferation, migration, and NOD/SCID repopulation.
Blood. 2004 Apr 15;103(8):2942-9. doi: 10.1182/blood-2003-07-2607. Epub 2003 Dec 24.
7
The essential roles of the chemokine SDF-1 and its receptor CXCR4 in human stem cell homing and repopulation of transplanted immune-deficient NOD/SCID and NOD/SCID/B2m(null) mice.
Leukemia. 2002 Oct;16(10):1992-2003. doi: 10.1038/sj.leu.2402684.
8
A point mutation that confers constitutive activity to CXCR4 reveals that T140 is an inverse agonist and that AMD3100 and ALX40-4C are weak partial agonists.
J Biol Chem. 2002 Jul 5;277(27):24515-21. doi: 10.1074/jbc.M200889200. Epub 2002 Mar 28.
9
Agonist-induced conformational changes in the G-protein-coupling domain of the beta 2 adrenergic receptor.
Proc Natl Acad Sci U S A. 2001 May 22;98(11):5997-6002. doi: 10.1073/pnas.101126198. Epub 2001 May 15.
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Five isoforms of the phosphatidylinositol 3-kinase regulatory subunit exhibit different associations with receptor tyrosine kinases and their tyrosine phosphorylations.
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