The fusion of bone-marrow-derived proinsulin-expressing cells with nerve cells underlies diabetic neuropathy
The fusion of bone-marrow-derived proinsulin-expressing cells with nerve cells underlies diabetic neuropathy
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DOI：
10.1073/pnas.0505717102
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发表时间：
2005-08-30
影响因子：
11.1
通讯作者：
Chan, L
中科院分区：
文献类型：
--
作者：
Terashima, T;Kojima, H;Chan, L
糖尿病神经病变是糖尿病最常见的微血管并发症。在此，我们发现，在含有链脲佐菌素的糖尿病啮齿动物的神经病变中，以胰岛素原表达为标志的一群骨髓来源的细胞迁移到坐骨神经和背根节(DRG)中的神经元并与其融合，导致神经元功能障碍和加速细胞凋亡。识别融合细胞的胰岛素原表达的缺失或存在，而不是分离出DRG神经元的大鼠的疾病状态(非糖尿病与糖尿病)决定了DRG神经元显示正常或异常的钙稳态和凋亡。这些结果提示，骨髓来源的细胞可能在糖尿病并发症的发病机制中起重要作用。
Diabetic neuropathy is the most common microvascular complication of diabetes. Here we show that, in streptozotocin-incluced diabetic rodents with neuropathy, a subpopulation of bone-marrow-derived cells marked by proinsulin expression migrates to and fuses with neurons in the sciatic nerve and dorsal root ganglion (DRG), resulting in neuronal dysfunction and accelerated apoptosis. The absence or presence of proinsulin expression, which identifies the fusion cells, and not the disease state (nondiabetic vs. diabetic) of the rats from which the DRG neurons are isolated determines whether the DRG neurons show normal or abnormal calcium homeostasis and apoptosis. These results suggest that bone-marrow-derived cells may play an important role in the pathogenesis of diabetic complications.