Department of Histology and Embryology, Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing, P.R. China.
Eur Rev Med Pharmacol Sci. 2019 Apr;23(7):3012-3020. doi: 10.26355/eurrev_201904_17583.
Demyelinating neurodegenerative diseases are some of the most important neurological diseases that threaten the health of the elderly. Astrocytes (ASTs) play an important role in the regulation of the growth and development of oligodendrocytes (OLs) and oligodendrocyte progenitor cells (OPCs), which participate in remyelination. This study investigated the mechanism by which ASTs promote the proliferation of OPCs via connexin 47 (Cx47) in OPCs.
Under direct-contact co-culture conditions, we performed Cx47 siRNA interference in ASTs and OPCs and tested the cell proliferation ability by flow cytometry and with 5-ethynyl-20-deoxyuridine (EdU). We then detected Chi3l1 expression by Western blotting and immunofluorescence. Next, after the addition of exogenous Chi3l1 protein to OPCs under monoculture conditions, we tested the cell proliferation ability by flow cytometry and EdU.
After siRNA interference with Cx47, the expression of Chi3l1 decreased from 1.10±0.91 to 0.30±0.08, and the proportion of new OPCs decreased from 48.7±3.8% to 28.4±6.6%. Moreover, upon addition of exogenous Chi3l1 protein under OPCs mono-culture conditions, the expression of cyclin D1 increased from 0.68±0.09 to 1.16±0.14, leading to an increased number of OPCs in the S phase, from 7.37±1.38% to 13.55±1.60%.
Cx47/Chi3l1 plays an important role in the promotion of OPCs proliferation by ASTs. ASTs can promote the expression of Chi3l1 via Cx47 in OPCs, and then activate the expression of cyclin D1 and regulate the cell cycle of OPCs, thereby promoting cell proliferation. This study provides a new target for the treatment of neurodegenerative diseases.
脱髓鞘神经退行性疾病是威胁老年人健康的最重要的神经疾病之一。星形胶质细胞（ASTs）在调节少突胶质细胞（OLs）和少突胶质前体细胞（OPCs）的生长和发育中起重要作用，参与髓鞘的修复。本研究探讨了星形胶质细胞通过缝隙连接蛋白 47（Cx47）在少突胶质前体细胞中促进其增殖的机制。
在直接接触共培养条件下，我们对星形胶质细胞和少突胶质前体细胞进行 Cx47 siRNA 干扰，并通过流式细胞术和 5-乙炔基-20-脱氧尿苷（EdU）检测细胞增殖能力。然后，通过 Western blot 和免疫荧光检测 Chi3l1 表达。接着，在单核培养条件下向少突胶质前体细胞中添加外源性 Chi3l1 蛋白后，通过流式细胞术和 EdU 检测细胞增殖能力。
Cx47 沉默后，Chi3l1 的表达从 1.10±0.91 降至 0.30±0.08，新的少突胶质前体细胞比例从 48.7±3.8%降至 28.4±6.6%。此外，在单核培养条件下添加外源性 Chi3l1 蛋白后，cyclin D1 的表达从 0.68±0.09 增加到 1.16±0.14，导致 S 期少突胶质前体细胞数量从 7.37±1.38%增加到 13.55±1.60%。
Cx47/Chi3l1 在星形胶质细胞促进少突胶质前体细胞增殖中起重要作用。星形胶质细胞可以通过 Cx47 在少突胶质前体细胞中促进 Chi3l1 的表达，进而激活 cyclin D1 的表达并调节少突胶质前体细胞的细胞周期，从而促进细胞增殖。本研究为神经退行性疾病的治疗提供了新的靶点。
