Xia Maosheng, Zhu Yue
Department of Orthopaedics, The First Hospital of China Medical University, No. 155 Nanjing Bei Street Heping District, Shenyang, People's Republic of China, 110001.
J Mol Neurosci. 2015 Jan;55(1):131-140. doi: 10.1007/s12031-014-0393-5. Epub 2014 Aug 13.
After spinal cord injury (SCI), the level of adenosine triphosphate (ATP) and extracellular matrix (ECM) is increased. Formation of the glial scar is a complex process that is primarily attributed to astrocytic proliferation, and the fibrotic scar results from ECM deposition. In our previous researches, ATP and fibronectin was able to separately stimulate the proliferation of astrocytes. Moreover, fibronectin increases the expression of P2Y1 receptor and offers more binding sites for ATP, which aggravates the proliferation. Meanwhile, ATP was also able to stimulate the release of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α), but fibronectin does not. Recently, it has been reported that over-expressing P2Y1 receptor could promote the level of Sox9. However, the regulation of Sox genes by ATP is still little known in spinal cord astrocytes. In the present study, we discovered that ATP was able to increase the expression of Sox2 and Sox9; fibronectin did not have this direct function. Sox9 was only involved in the proliferation increased by ATP, and Sox2 influenced the release of IL-6 stimulated by ATP. Understanding the critical role of Sox2 and Sox9 mediated by ATP may provide a potential target for therapeutic intervention in spinal cord injury.
脊髓损伤（SCI）后，三磷酸腺苷（ATP）水平和细胞外基质（ECM）会升高。胶质瘢痕的形成是一个复杂的过程，主要归因于星形胶质细胞的增殖，而纤维化瘢痕则是由ECM沉积导致的。在我们之前的研究中，ATP和纤连蛋白能够分别刺激星形胶质细胞的增殖。此外，纤连蛋白会增加P2Y1受体的表达，并为ATP提供更多的结合位点，从而加剧增殖。同时，ATP还能够刺激白细胞介素（IL）-6和肿瘤坏死因子-α（TNF-α）的释放，但纤连蛋白则不会。最近，有报道称过表达P2Y1受体可提高Sox9的水平。然而，在脊髓星形胶质细胞中，ATP对Sox基因的调控仍鲜为人知。在本研究中，我们发现ATP能够增加Sox2和Sox9的表达；纤连蛋白没有这种直接作用。Sox9仅参与由ATP增加的增殖过程，而Sox2则影响由ATP刺激的IL-6的释放。了解ATP介导的Sox2和Sox9的关键作用可能为脊髓损伤的治疗干预提供一个潜在靶点。
