Differentiating Glomerular Inflammation from Fibrosis in a Bone Marrow Chimera for Rat Anti-Glomerular Basement Membrane Glomerulonephritis.
Differentiating Glomerular Inflammation from Fibrosis in a Bone Marrow Chimera for Rat Anti-Glomerular Basement Membrane Glomerulonephritis.
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DOI：
10.1159/000438929
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发表时间：
2015
影响因子：
4.2
通讯作者：
Lou Y
中科院分区：
文献类型：
--
作者：
Zhou C;Lou K;Tatum K;Funk J;Wu J;Bartkowiak T;Kagan D;Lou Y
许多类型的肾小球肾炎（GN）经历串联连接阶段：炎症和纤维化。人类GNs的纤维化导致不可逆转的终末期疾病。本研究探讨了如何控制这两个阶段。采用大鼠抗肾小球基底膜（GBM） GN模型，建立GN耐药Lewis （LEW）大鼠与GN敏感Wistar Kyoto （WKY）大鼠骨髓嵌合体。嵌合体间肾小球炎症和纤维化的比较。无论是否与宿主WKY的T细胞共转移，LEW的BM到WKY （WKYLEW）嵌合体都具有gn抗性。另一方面，WKY的BM - LEW （LEWWKY）嵌合体免疫后出现肾小球炎症和蛋白尿。定量分析显示免疫后的LEWWKY嵌合体肾小球炎症细胞的数量和组成与免疫后的WKY大鼠炎症峰值相似。因此，肾小球炎症由BM衍生的非t细胞群控制。然而，与WKY大鼠不同的是，LEWWKY大鼠尽管存在持续的炎症和蛋白尿，但直到实验结束（84天）才发生纤维化。炎症本身不足以引发纤维化，提示肾小球细胞在纤维化过程中起关键作用。由于LEWWKY嵌合体允许我们将肾小球炎症与纤维化分离，该模型为研究炎症后纤维化如何启动提供了有用的工具。
Many types of glomerulonephritis (GN) undergo tandem connected phases: inflammation and fibrosis. Fibrosis in human GNs leads to irreversible end stage disease. This study investigated how these two phases were controlled. Using a rat anti-glomerular basement membrane (GBM) GN model, we established bone marrow (BM) chimeras between GN-resistant Lewis (LEW) and GN-susceptible Wistar Kyoto (WKY) rats. Glomerular inflammation and fibrosis were compared between chimeras. LEW’s BM to WKY (WKYLEW) chimeras with or without co-transfer of host WKY’s T cells were GN-resistant. On the other hand, WKY’s BM to LEW (LEWWKY) chimeras developed glomerular inflammation and albuminuria upon immunization. Quantitative analysis showed that the number and composition of inflammatory cells in glomeruli of immunized LEWWKY chimeras were similar to those in immunized WKY rats at their inflammatory peak. Thus, glomerular inflammation was controlled by BM derived non-T cell populations. However, unlike WKY rats, LEWWKY rats did not develop fibrosis until the end of experiments (84 days) in spite of persistent inflammation and albuminuria. Inflammation alone was not sufficient to trigger fibrosis, suggesting a critical role of glomerular cells in the fibrotic process. As LEWWKY chimera allows us to separate glomerular inflammation from fibrosis, this model provides a useful tool to study how fibrosis is initiated following inflammation.