Systematic implantation of dedifferentiated fat cells ameliorated monoclonal antibody 1-22-3-induced glomerulonephritis by immunosuppression with increases in TNF-stimulated gene 6.
Systematic implantation of dedifferentiated fat cells ameliorated monoclonal antibody 1-22-3-induced glomerulonephritis by immunosuppression with increases in TNF-stimulated gene 6.
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DOI：
10.1186/s13287-015-0069-2
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发表时间：
2015-04-16
影响因子：
7.5
通讯作者：
Kawachi H
中科院分区：
文献类型：
--
作者：
Maruyama T;Fukuda N;Matsumoto T;Kano K;Endo M;Kazama M;Kazama T;Ikeda J;Matsuda H;Ueno T;Abe M;Okada K;Soma M;Matsumoto K;Kawachi H
间充质干细胞（MSCs）的植入最近已被报道通过抗炎和免疫抑制作用修复组织损伤。我们建立了去分化脂肪（DFAT）细胞，表现出与MSC相同的特性。本实验观察了经肾动脉或尾静脉输注106个DFAT细胞对单克隆抗体（mAb）1-22-3诱导的大鼠肾小球肾炎（免疫性肾损伤）和阿霉素诱导的大鼠肾病（非免疫性肾损伤）的影响。注射mAb 1-22-3的大鼠还通过尾静脉植入106 μ L转染有TSG-6 siRNA的DFAT细胞。尽管通过尾静脉输注到血液循环中的DFAT细胞主要滞留在肺中而没有到达肾脏，但DFAT细胞的植入减少了蛋白尿并改善了肾小球硬化和间质纤维化。DFAT细胞通过尾静脉植入显着降低肾损伤分子-1，IV型胶原和纤连蛋白mRNA的表达，而nephrin mRNA的表达增加。DFAT细胞植入并不能改善阿霉素肾病，但能显著减少巨噬细胞、普通白细胞和泛T细胞的肾小球内流。然而，辅助性T细胞的肾小球内流增加。DFAT细胞移植降低了mAb 1-22-3注射大鼠肾皮质中白细胞介素（IL）-6和IL-12β mRNA的表达，并增加了TNF刺激基因（TSG）-6 mRNA的表达。DFAT细胞中TSG-6蛋白的基础水平显著高于成纤维细胞。与DFAT细胞共培养的MCs中TSG-6 mRNA的表达显著高于单独的系膜细胞或DFAT细胞。通过尾静脉系统植入DFAT细胞与TSG-6 siRNA没有改善mAb 1-22-3注射大鼠的蛋白尿、肾功能不全和肾变性。DFAT细胞的系统植入通过免疫抑制作用有效地改善了mAb 1-22-3诱导的肾小球肾炎，伴随着巨噬细胞浸润和IL-6、IL-10和IL-12β表达的抑制，并增加了血清和肾脏TSG-6的产生，这通过TSG-6的免疫抑制作用改善了mAb 1- 22 -3诱导的肾脏变性。因此，DFAT细胞将是用于治疗免疫性进行性肾病的合适的细胞来源。本文的在线版本（doi：10.1186/s13287-015-0069-2）包含补充材料，可供授权用户使用。
Implantation of mesenchymal stem cells (MSCs) has recently been reported to repair tissue injuries through anti-inflammatory and immunosuppressive effects. We established dedifferentiated fat (DFAT) cells that show identical characteristics to MSCs. We examined the effects of 106 of DFAT cells infused through renal artery or tail vein on monoclonal antibody (mAb) 1-22-3-induced glomerulonephritis (as an immunological type of renal injury) and adriamycin-induced nephropathy (as a non-immunological type of renal injury) in rats. The mAb 1-22-3-injected rats were also implanted with 106 of DFAT cells transfected with TSG-6 siRNA through tail vein. Although DFAT cells transfused into blood circulation through the tail vein were trapped mainly in lungs without reaching the kidneys, implantation of DFAT cells reduced proteinuria and improved glomerulosclerosis and interstitial fibrosis. Implantation of DFAT cells through the tail vein significantly decreased expression of kidney injury molecule-1, collagen IV and fibronectin mRNAs, whereas nephrin mRNA expression was increased. Implantation of DFAT cells did not improve adriamycin-induced nephropathy, but significantly decreased the glomerular influx of macrophages, common leukocytes and pan T cells. However, the glomerular influx of helper T cells, was increased. Implantation of DFAT cells decreased expression of interleukin (IL)-6 and IL-12β mRNAs and increased expression of TNF-stimulated gene (TSG)-6 mRNA in renal cortex from mAb 1-22-3-injected rats. The basal level of TSG-6 protein was significantly higher in DFAT cells than in fibroblasts. Expression of TSG-6 mRNA in MCs cocultured with DFAT cells was significantly higher than in mesangial cells or DFAT cells alone. Systematic implantation of DFAT cells with TSG-6 siRNA through tail vein did not improve proteinuria, renal dysfunction and renal degeneration in the mAb 1-22-3-injected rats. Systematic implantation of DFAT cells effectively ameliorated mAb 1-22-3-induced glomerulonephritis through immunosuppressive effects accompanied by the suppression of macrophage infiltration and expression of IL-6, IL-10 and IL-12β, and increased production of serum and renal TSG-6 that improved the mAb 1-22-3-induced renal degeneration by the immunosuppressive effects of TSG-6. Thus DFAT cells will be suitable cell source for the treatment of immunological progressive renal diseases. The online version of this article (doi:10.1186/s13287-015-0069-2) contains supplementary material, which is available to authorized users.
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影响因子：
5.2
作者：
Mitchell, James B.;McIntosh, Kevin;Gimble, Jeffrey M.
通讯作者：
Gimble, Jeffrey M.
影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Prockop, Darwin J.
影响因子：
2.4
作者：
Liu, Hui;Chen, Yinkui;Liu, Qifa
通讯作者：
Liu, Qifa