Implantation of dedifferentiated fat cells ameliorated antineutrophil cytoplasmic antibody glomerulonephritis by immunosuppression and increases in tumor necrosis factor-stimulated gene-6.
Implantation of dedifferentiated fat cells ameliorated antineutrophil cytoplasmic antibody glomerulonephritis by immunosuppression and increases in tumor necrosis factor-stimulated gene-6.
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DOI：
10.1186/s13287-022-03014-8
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发表时间：
2022-07-16
影响因子：
7.5
通讯作者：
中科院分区：
文献类型：
--
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去分化脂肪（DFAT）细胞的植入具有免疫抑制作用。为了开发DFAT细胞治疗抗中性粒细胞胞浆抗体（ANCA）肾小球肾炎的方法，研究了DFAT细胞移植对小鼠ANCA肾小球肾炎的影响。pkh26标记的DFAT细胞（105）经眶后静脉丛输注，观察DFAT细胞在ICR小鼠体内的传递情况。DFAT细胞（105）也被植入SCG小鼠作为ANCA肾小球肾炎模型。检测肾脏组织中肿瘤坏死因子刺激基因-6 (TSG-6) mRNA和蛋白的表达，分析血浆、肺和肾脏组织中与TSG-6相关的microrna的表达。检测了DFAT移植SCG小鼠肾脏中CD44、前列腺素（PG） E2、白细胞介素(IL)-10、IL-1β、肿瘤坏死因子(TNF)-α mrna、C-C基元趋化因子配体17 （CCL-17）和单核细胞趋化蛋白(MCP)-1蛋白的表达。在静脉输注后，几乎所有的DFAT细胞都被困在肺部，而不是被输送到肾脏。移植DFAT细胞抑制SCG小鼠肾小球月牙形成，减少尿蛋白排泄，增加肾脏中TSG-6 mRNA、蛋白和免疫染色的表达。血浆、肾、肺组织中microRNA 23b-3p表达增加；CD44 mRNA表达降低；PGE2和IL-10 mrna在这些小鼠肾脏中的表达也增加。DFAT细胞的植入降低了SCG小鼠肾脏中TNF-α和MCP-1蛋白的表达，增加了CCL-17蛋白的表达。植入DFAT细胞的SCG小鼠的存活率高于未植入的SCG小鼠。ANCA型肾小球肾炎的改善机制与TSG-6的免疫抑制作用和M1-M2巨噬细胞的转化有关，提示DFAT细胞植入可能成为ANCA型肾小球肾炎的一种细胞治疗方法。在线版本包含补充材料，下载地址：10.1186/s13287-022-03014-8。
The implantation of dedifferentiated fat (DFAT) cells has been shown to exert immunosuppressive effects. To develop DFAT cell therapy for antineutrophil cytoplasmic antibody (ANCA) glomerulonephritis, the effects of the implantation of DFAT cells on ANCA glomerulonephritis were investigated in mice. PKH26-labeled DFAT cells (105) were infused through the posterior orbital venous plexus to investigate delivery of DFAT cells in ICR mice. DFAT cells (105) were also implanted in SCG mice as a model for ANCA glomerulonephritis. Expression of tumor necrosis factor-stimulated gene-6 (TSG-6) mRNA and protein in kidney was evaluated, and the expression of microRNAs associated with TSG-6 in plasma, lung and kidney was analyzed. Expressions of CD44, prostaglandin (PG) E2, interleukin (IL)-10, IL-1β, tumor necrosis factor (TNF)-α mRNAs, C–C motif chemokine ligand 17 (CCL-17) and monocyte chemoattractant protein (MCP)-1 proteins were measured in kidney from SCG mice implanted with DFAT cells. After their intravenous infusion, almost all DFAT cells were trapped in the lung and not delivered into the kidney. Implantation of DFAT cells in SCG mice suppressed glomerular crescent formation, decreased urinary protein excretions and increased expression of TSG-6 mRNA, protein and immunostaining in kidney from these mice. Increased expression of microRNA 23b-3p in plasma, kidney and lung; decreased expression of CD44 mRNA; and increased expression of PGE2 and IL-10 mRNAs were also observed in kidney from these mice. Implantation of DFAT cells also decreased the expression of TNF-α and MCP-1 proteins and increased that of CCL-17 protein in kidney from the SCG mice. Survival rates were higher in SCG mice implanted with DFAT cells than in SCG mice without implantation. Mechanisms underlying the effects of improvement of ANCA glomerulonephritis are associated with immunosuppressive effects by TSG-6 and the transition of M1–M2 macrophages, suggesting that implantation of DFAT cells may become a cell therapy for ANCA glomerulonephritis. The online version contains supplementary material available at 10.1186/s13287-022-03014-8.
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影响因子：
20.3
作者：
Sato, Kazuya;Ozaki, Katsutoshi;Ozawa, Keiya
通讯作者：
Ozawa, Keiya
影响因子：
7.5
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
通讯作者：
Kawachi H
影响因子：
12.3
作者：
Robinson MD;Oshlack A
通讯作者：
Oshlack A
影响因子：
29.4
作者：
Sala, Emanuela;Genua, Marco;Vetrano, Stefania
通讯作者：
Vetrano, Stefania
影响因子：
--
作者：
Jennette, J. C.;Falk, R. J.;Watts, R. A.
通讯作者：
Watts, R. A.