Following spinal cord injury (SCI), reactive astrocytes in the glial scar produce high levels of chondroitin sulfate proteoglycans (CSPGs), which are known to inhibit axonal regeneration. Transforming growth factor beta (TGFβ) is a well-known factor that induces the production of CSPGs, and in this study, we report a novel mechanism underlying TGFβ’s effects on CSPG secretion in primary rat astrocytes. We observed increased TGFβ-induced secretion of the CSPGs neurocan and brevican, and this occurred simultaneously with inhibition of autophagy flux. In addition, we show that neurocan and brevican levels are further increased when TGFβ is administered in the presence of an autophagy inhibitor, Bafilomycin-A1, while they are reduced when cells are treated with a concentration of rapamycin that is not sufficient to induce autophagy. These findings suggest that TGFβ mediates its effects on CSPG secretion through autophagy pathways. They also represent a potential new approach to reduce CSPG secretion in vivo by targeting autophagy pathways, which could improve axonal regeneration after SCI.

脊髓损伤 (SCI) 后，胶质瘢痕中的反应性星形胶质细胞会产生高水平的硫酸软骨素蛋白多糖 (CSPG)，已知其可抑制轴突再生。转化生长因子 β (TGFβ) 是一种众所周知的诱导 CSPG 产生的因子，在本研究中，我们报告了 TGFβ 对原代大鼠星形胶质细胞 CSPG 分泌影响的新机制。我们观察到 TGFβ 诱导的 CSPGs neurocan 和 brevican 分泌增加，这与自噬通量的抑制同时发生。此外，我们发现在自噬抑制剂 Bafilomycin-A1 存在的情况下给予 TGFβ 时，neurocan 和 brevican 水平会进一步增加，而当细胞用不足以诱导自噬的雷帕霉素浓度处理时，它们会降低。这些发现表明TGFβ通过自噬途径介导其对CSPG分泌的影响。它们还代表了一种通过靶向自噬途径减少体内 CSPG 分泌的潜在新方法，这可以改善 SCI 后的轴突再生。