Hypoxic preconditioning enhances bone marrow mesenchymal stem cell migration via Kv2.1 channel and FAK activation
Hypoxic preconditioning enhances bone marrow mesenchymal stem cell migration via Kv2.1 channel and FAK activation
复制标题
DOI：
10.1152/ajpcell.00013.2010
复制
发表时间：
2011-08-01
影响因子：
5.5
通讯作者：
Yu, Shan Ping
中科院分区：
文献类型：
--
作者：
Hu, Xinyang;Wei, Ling;Yu, Shan Ping
Hu X，Wei L，Taylor TM，Wei J，Zhou X，Wang J，Yu SP.低氧预处理通过Kv2.1通道和FAK激活增强骨髓间充质干细胞迁移。美国生理学杂志细胞生理学301：C362-C372，2011年。首次发表于2011年5月11日; doi：10.1152/ajpcell.00013.2010。骨髓间充质干细胞（BMSCs）是一种重要的干细胞移植技术，是治疗心脏和大脑缺血性疾病的有效手段。移植细胞的迁移能力是组织修复的关键细胞功能。基于我们最近的观察，即低氧预处理（HP）在改善干细胞治疗中具有多种益处，并且钾离子Kv2.1通道作为粘着斑激酶（FAK）激活和细胞运动的促进剂，本研究验证了HP处理可以通过增加Kv2.1表达和FAK活性的机制来增加BMSC迁移的假设。将来源于绿色荧光蛋白转基因小鼠的BMSC在常氧（N-BMSC）或缺氧（0.5%O-2）（HP-BMSC）条件下处理24 h。Western blot分析显示HP选择性上调Kv2.1的表达，而其他K+通道，如Kv1.5和Kv1.4，不受影响。与常氧对照组相比，HP-BMSCs记录到明显更大的外向延迟整流钾电流。HP可增强BMSC在体外和静脉移植到永久性心肌梗死（MI）大鼠后的迁移/归巢活性。HP促进的BMSC迁移通过阻断K+通道或敲低Kv2.1来抑制。支持HP，Kv2.1和FAK激活之间的关系，HP增加FAK 397和FAK 576/577的磷酸化，这种作用被阻断K+通道拮抗。这些发现提供了新的证据，HP增强了BMSC迁移和归巢到损伤区域的能力;这种作用是通过Kv2.1对FAK磷酸化/活化的调节作用介导的。
Hu X, Wei L, Taylor TM, Wei J, Zhou X, Wang J, Yu SP. Hypoxic preconditioning enhances bone marrow mesenchymal stem cell migration via Kv2.1 channel and FAK activation. Am J Physiol Cell Physiol 301: C362-C372, 2011. First published May 11, 2011; doi: 10.1152/ajpcell.00013.2010.-Transplantation using stem cells including bone marrow mesenchymal stem cells (BMSCs) is emerging as a potential regenerative therapy after ischemic attacks in the heart and brain. The migration capability of transplanted cells is a critical cellular function for tissue repair. Based on our recent observations that hypoxic preconditioning (HP) has multiple benefits in improving stem cell therapy and that the potassium Kv2.1 channel acts as a promoter for focal adhesion kinase (FAK) activation and cell motility, the present investigation tested the hypothesis that HP treatment can increase BMSC migration via the mechanism of increased Kv2.1 expression and FAK activities. BMSCs derived from green fluorescent protein-transgenic mice were treated under either normoxic (N-BMSC) or hypoxic (0.5% O-2) (HP-BMSC) conditions for 24 h. Western blot analysis showed HP selectively upregulated Kv2.1 expression while leaving other K+ channels, such as Kv1.5 and Kv1.4, unaffected. Compared with normoxic controls, significantly larger outward delayed rectifier K+ currents were recorded in HP-BMSCs. HP enhanced BMSC migration/homing activities in vitro and after intravenous transplantation into rats subjected to permanent myocardial infarction (MI). The HP-promoted BMSC migration was inhibited by either blocking K+ channels or knocking down Kv2.1. Supporting a relationship among HP, Kv2.1, and FAK activation, HP increased phosphorylation of FAK397 and FAK576/577, and this effect was antagonized by blocking K+ channels. These findings provide novel evidence that HP enhances the ability of BMSCs to migrate and home to the injured region; this effect is mediated through a regulatory role of Kv2.1 on FAK phosphorylation/activation.