Huang Weiyi, Lv Bingke, Zeng Huijun, Shi Dandan, Liu Yi, Chen Fanfan, Li Feng, Liu Xinghui, Zhu Rong, Yu Lei, Jiang Xiaodan
The National Key Clinic Specialty, The Neurosurgery Institute of Guangdong Province, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Department of Anatomy, Key Laboratory of Construction and Detection of Guangdong Province, Southern Medical University, Guangzhou, China.
J Cell Physiol. 2015 Oct;230(10):2461-75. doi: 10.1002/jcp.24981.
Astrocytes are critical for ischemic stroke, and understanding their role in mesenchymal stem cell (MSC)-mediated protection against ischemic injury is important. The paracrine capacity of MSCs has been proposed as the principal mechanism contributing to the protection and repair of brain tissue. In the present study, an in vitro oxygen-glucose deprivation (OGD) model was used to mimic ischemic injury. OGD-induced astrocytes were reperfused with MSC-conditioned medium (MSC-CM) or co-cultured with MSCs for 24 h to create an environment abundant in paracrine factors. The results indicated that both situations could protect astrocytes from apoptosis, increase cell metabolic activity, and reduce glial fibrillary acidic protein (GFAP) overexpression; however, the effects of co-culturing with MSCs were more positive. Paracrine factors suppressed the activation of p38 MAPK, JNK, and their downstream targets p53 and STAT1. Inhibition of p38 MAPK, JNK, p53, and STAT1 attenuated astrocyte injury and/or GFAP upregulation. Activation of p38 MAPK and JNK suppressed the beneficial effects of paracrine factors, resulting in decreased survival and GFAP overexpression. These results suggest that paracrine factors inhibit p38 MAPK and JNK, and most likely by regulating their downstream targets, p53 and STAT1, to promote astrocyte survival associated with GFAP downregulation after ischemic stroke in vitro.
星形胶质细胞对缺血性中风至关重要，了解它们在间充质干细胞（MSC）介导的缺血性损伤保护中的作用很重要。MSC的旁分泌能力被认为是促进脑组织保护和修复的主要机制。在本研究中，使用体外氧糖剥夺（OGD）模型模拟缺血性损伤。将OGD诱导的星形胶质细胞用MSC条件培养基（MSC-CM）再灌注或与MSC共培养24小时，以创造一个富含旁分泌因子的环境。结果表明，这两种情况都可以保护星形胶质细胞免于凋亡，增加细胞代谢活性，并减少胶质纤维酸性蛋白（GFAP）的过度表达；然而，与MSC共培养的效果更积极。旁分泌因子抑制p38 MAPK、JNK及其下游靶点p53和STAT1的激活。抑制p38 MAPK、JNK、p53和STAT1可减轻星形胶质细胞损伤和/或GFAP上调。激活p38 MAPK和JNK可抑制旁分泌因子的有益作用，导致存活率降低和GFAP过度表达。这些结果表明，旁分泌因子抑制p38 MAPK和JNK，很可能是通过调节其下游靶点p53和STAT1，以促进体外缺血性中风后与GFAP下调相关的星形胶质细胞存活。
