Zhou Cindy, Lou Kristie, Tatum Kiana, Funk Jeremiah, Wu Jean, Bartkowiak Todd, Kagan David, Lou Yahuan
Am J Nephrol. 2015;42(1):42-53. doi: 10.1159/000438929.
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 2 phases were controlled.
Using a rat anti-glomerular basement membrane 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 chimeras with or without co-transfer of host WKY's T cells were GN-resistant. On the other hand, WKY's BM to LEW (LEW(WKY)) chimeras developed glomerular inflammation and albuminuria upon immunization. Quantitative analysis showed that the number and composition of inflammatory cells in glomeruli of immunized LEW(WKY) 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, LEW(WKY) 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 LEW(WKY) chimera allows us to separate glomerular inflammation from fibrosis, this model provides a useful tool to study how fibrosis is initiated following inflammation.
许多类型的肾小球肾炎（GN）经历炎症和纤维化这两个连续的阶段。人类肾小球肾炎中的纤维化会导致不可逆转的终末期疾病。本研究调查了这两个阶段是如何被控制的。
使用大鼠抗肾小球基底膜肾小球肾炎模型，我们在抗GN的Lewis（LEW）大鼠和易感GN的Wistar Kyoto（WKY）大鼠之间建立了骨髓（BM）嵌合体。比较嵌合体之间的肾小球炎症和纤维化情况。
带有或不带有宿主WKY大鼠T细胞共转移的LEW骨髓至WKY嵌合体对GN具有抗性。另一方面，WKY骨髓至LEW（LEW（WKY））嵌合体在免疫后出现肾小球炎症和蛋白尿。定量分析表明，免疫后的LEW（WKY）嵌合体肾小球中炎症细胞的数量和组成与免疫后的WKY大鼠在炎症高峰期时相似。因此，肾小球炎症由骨髓来源的非T细胞群体控制。然而，与WKY大鼠不同，尽管存在持续的炎症和蛋白尿，LEW（WKY）大鼠直到实验结束（84天）都没有发生纤维化。
仅炎症不足以引发纤维化，这表明肾小球细胞在纤维化过程中起关键作用。由于LEW（WKY）嵌合体使我们能够将肾小球炎症与纤维化分开，该模型为研究炎症后纤维化如何启动提供了一个有用的工具。
