SHP-2 通过 Akt 和 ERK1/2 信号通路促进体外少突胶质前体细胞的成熟。

SHP-2 promotes the maturation of oligodendrocyte precursor cells through Akt and ERK1/2 signaling in vitro.

机构信息

Key Laboratory of Molecular Neurobiology, Institute of Neuroscience, Ministry of Education, Neuroscience Research Centre of Changzheng Hospital, Second Military Medical University, Shanghai, China.

出版信息

PLoS One. 2011;6(6):e21058. doi: 10.1371/journal.pone.0021058. Epub 2011 Jun 20.

BACKGROUND

Oligodendrocyte precursor cells (OPCs) differentiate into oligodendrocytes (OLs), which are responsible for myelination. Myelin is essential for saltatory nerve conduction in the vertebrate nervous system. However, the molecular mechanisms of maturation and myelination by oligodendrocytes remain elusive.

METHODS AND FINDINGS

In the present study, we showed that maturation of oligodendrocytes was attenuated by sodium orthovanadate (a comprehensive inhibitor of tyrosine phosphatases) and PTPi IV (a specific inhibitor of SHP-2). It is also found that SHP-2 was persistently expressed during maturation process of OPCs. Down-regulation of endogenous SHP-2 led to impairment of oligodendrocytes maturation and this effect was triiodo-L-thyronine (T3) dependent. Furthermore, over-expression of SHP-2 was shown to promote maturation of oligodendrocytes. Finally, it has been identified that SHP-2 was involved in activation of Akt and extracellular-regulated kinases 1 and 2 (ERK1/2) induced by T3 in oligodendrocytes.

CONCLUSIONS

SHP-2 promotes oligodendrocytes maturation via Akt and ERK1/2 signaling in vitro.

背景

少突胶质前体细胞（OPCs）分化为少突胶质细胞（OLs），后者负责髓鞘形成。髓鞘对于脊椎动物神经系统中的跳跃式神经传导至关重要。然而，少突胶质细胞成熟和髓鞘形成的分子机制仍不清楚。

方法和发现

在本研究中，我们表明，正钒酸钠（酪氨酸磷酸酶的综合抑制剂）和 PTPiIV（SHP-2 的特异性抑制剂）可减弱少突胶质细胞的成熟。还发现 SHP-2 在 OPCs 的成熟过程中持续表达。内源性 SHP-2 的下调导致少突胶质细胞成熟受损，这种作用依赖于三碘甲状腺原氨酸（T3）。此外，过表达 SHP-2 可促进少突胶质细胞的成熟。最后，鉴定出 SHP-2 参与 T3 在少突胶质细胞中诱导的 Akt 和细胞外调节激酶 1 和 2（ERK1/2）的激活。