Chen Xiaoqing, Hao Jie, Fu Ting, Liu Jie, Yu Mingchen, He Shuang, Qian Rong, Zhang Feng
Department of Orthopedics, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.
Medical College, Nantong University, Nantong, 226001, Jiangsu, China.
Neurochem Res. 2016 Oct;41(10):2645-2654. doi: 10.1007/s11064-016-1977-y. Epub 2016 Jun 23.
Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), a well-characterized marker of stem cell and cancer stem cells (CSCs), is best known as a transmembrance receptor for increases canonical Wnt signaling amplitude. In addition, in some types of human cancers, LGR5 has been found to be overexpressed. However, the distribution and function of LGR5 in spinal cord injury (SCI) are still unknown. In this study, we examined LGR5 expression and cellular localization in rats following acute SCI. Western blot analysis and immunohistochemistry exhibited an important upregulation of LGR5 in injury spinal cord. Double immunofluorescence staining showed that LGR5 was co-expressed with glial fibrillary acidic protein (GFAP). Moreover, we detected that PCNA had colocalization with LGR5 and GFAP after SCI. In the vitro model, we could find the enhanced expression of LGR5 in the primary astrocyte which was induced by the lipopolysaccharide (LPS). In particular, we found the significantly decreased ability for proliferation when this LGR5-specific siRNA transfected primary astrocytes. In a word, this is the first description of LGR5 expression in spinal cord injury. These data indicated that LGR5 might be of great significance in CNS pathophysiology after SCI.
富含亮氨酸重复序列的G蛋白偶联受体5(LGR5)是一种已被充分表征的干细胞和癌症干细胞(CSC)标志物,最为人所知的是它作为一种跨膜受体可增强经典Wnt信号传导幅度。此外,在某些类型的人类癌症中,已发现LGR5过表达。然而,LGR5在脊髓损伤(SCI)中的分布和功能仍不清楚。在本研究中,我们检测了急性脊髓损伤后大鼠中LGR5的表达和细胞定位。蛋白质印迹分析和免疫组织化学显示损伤脊髓中LGR5有重要上调。双重免疫荧光染色表明LGR5与胶质纤维酸性蛋白(GFAP)共表达。此外,我们检测到脊髓损伤后增殖细胞核抗原(PCNA)与LGR5和GFAP共定位。在体外模型中,我们发现脂多糖(LPS)诱导的原代星形胶质细胞中LGR5表达增强。特别是,当用这种LGR5特异性小干扰RNA转染原代星形胶质细胞时,我们发现其增殖能力显著下降。总之,这是首次描述脊髓损伤中LGR5的表达。这些数据表明LGR5在脊髓损伤后的中枢神经系统病理生理学中可能具有重要意义。