Role of bone marrow cells in the healing process of mouse experimental glomerulonephritis
Role of bone marrow cells in the healing process of mouse experimental glomerulonephritis
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DOI：
10.1203/01.pdr.0000169997.45684.05
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发表时间：
2005-08-01
影响因子：
3.6
通讯作者：
Fukunaga, Y
中科院分区：
文献类型：
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作者：
Hayakawa, M;Ishizaki, M;Fukunaga, Y
最近的研究表明，骨髓（BM）细胞分化成各种细胞类型，从而参与受损器官的重建。在本研究中，我们研究了在从实验诱导的肾炎中恢复的过程中，BM来源的细胞被纳入肾小球的程度。为了研究BM细胞在肾小球中的定位，通过将来自绿色荧光蛋白（GFP）转基因小鼠的BM细胞移植到野生型小鼠中来制备嵌合小鼠。5周后，静脉注射哈布蛇毒诱发肾小球肾炎。然后每隔几天处死一组小鼠，持续42天，收获的肾脏样品进行免疫组织化学和免疫电镜分析，目的是检测肾小球内GFP（+）细胞的存在。嵌合体动物注射哈布毒后1- 3d内发生增生性肾小球肾炎。42 d内病变逐渐消退，肾小球结构恢复正常。与病程一致，第1-3天肾小球内存在大量GFP（+）细胞，但到第7天大多数细胞消失。尽管如此，一些GFP（+）细胞仍然存在于肾小球内，显示系膜增生性变化，并被发现表达血栓调节蛋白（TM），一种特异性内皮细胞标记物。这些GFP-TM双阳性细胞占总肾小球核的1.31-2.24%，从第7天到第42天，水平保持稳定至少12个月。因此，似乎BM细胞可以产生参与肾小球重塑的内皮细胞。
Recent studies have shown bone marrow (BM) cells to differentiate into a variety of cell types and to thereby participate in the reconstitution of damaged organs. In the present study, we examined the extent to which BM-derived cells are incorporated into glomeruli during recovery from experimentally induced nephritis. To investigate the localization of BM cells in glomeruli, chimeric mice were prepared by transplanting BM cells from green fluorescent protein (GFP) transgenic mice into wild-type mice. Five weeks later, glomerulonephritis was induced by intravenous injection of Habu snake venom. Groups of mice were then killed every few days for 42 d, and harvested kidney samples were subjected to immunohistochemical and immunoelectron microscopic analyses with the aim of detecting the presence of GFP(+) cells within glomeruli. Chimeric animals injected with Habu venom developed proliferative glomerulonephritis within 1-3 d. The lesion gradually subsided and the glomerular structure returned to normal within 42 d. Consistent with the disease course, large numbers of GFP(+) cells were present within glomeruli on d 1-3, but most had disappeared by d 7. Nevertheless, some GFP(+) cells did remain within glomeruli showing mesangial proliferative changes, and were found to express thrombomodulin (TM), a specific endothelial cell marker. These GFP-TM-double-positive cells accounted for a mean of 1.31-2.24% of the total glomerular nuclei from d 7 through d 42, levels that remained stable for at least 12 mo. It thus appears that BM cells can give rise to endothelial cells that participate in the remodeling of glomeruli.