Molecular mechanisms governing the progression of nephritis in lupus prone mice and human lupus patients.
Molecular mechanisms governing the progression of nephritis in lupus prone mice and human lupus patients.
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DOI：
10.3389/fimmu.2023.1147526
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发表时间：
2023
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
病理性炎症是狼疮性肾炎（LN）肾脏损伤的主要驱动因素，但疾病进展的免疫机制和终末器官损伤的危险因素尚不清楚。为了通过LN的发展来表征分子谱，我们对狼疮易感小鼠NZM2328的微解剖肾脏进行了基因表达分析。我们检测了雄性小鼠和基因NZM2328。R27菌株作为确定慢性肾炎耐药机制的手段。比较了狼疮小鼠与人狼疮小鼠的基因表达谱。NZM2328小鼠表现出从急性到过渡性再到慢性肾小球肾炎（GN）的进展。每个阶段都表现出独特的分子特征。雄性小鼠和R27小鼠均未进入急性GN期，前者表现出最小的免疫浸润，后者表现出免疫调节基因特征的富集，同时显示出对细胞损伤的抵抗力。人类LN的基因表达谱与NZM2328小鼠相似，表明LN的进展阶段相似。总的来说，这项工作提供了涉及小鼠LN进展的免疫过程的全面检查，从而有助于我们了解终末期肾脏疾病的危险因素。此外，这项工作为改进LN的分类奠定了基础，并说明了小鼠模型在识别人类疾病阶段的适用性。
Pathologic inflammation is a major driver of kidney damage in lupus nephritis (LN), but the immune mechanisms of disease progression and risk factors for end organ damage are poorly understood. To characterize molecular profiles through the development of LN, we carried out gene expression analysis of microdissected kidneys from lupus-prone NZM2328 mice. We examined male mice and the congenic NZM2328.R27 strain as a means to define mechanisms associated with resistance to chronic nephritis. Gene expression profiles in lupus mice were compared with those in human LN. NZM2328 mice exhibited progress from acute to transitional and then to chronic glomerulonephritis (GN). Each stage manifested a unique molecular profile. Neither male mice nor R27 mice progressed past the acute GN stage, with the former exhibiting minimal immune infiltration and the latter enrichment of immunoregulatory gene signatures in conjunction with robust kidney tubule cell profiles indicative of resistance to cellular damage. The gene expression profiles of human LN were similar to those noted in the NZM2328 mouse suggesting comparable stages of LN progression. Overall, this work provides a comprehensive examination of the immune processes involved in progression of murine LN and thus contributes to our understanding of the risk factors for end-stage renal disease. In addition, this work presents a foundation for improved classification of LN and illustrates the applicability of murine models to identify the stages of human disease.
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影响因子：
14.9
作者：
Gene Ontology Consortium
通讯作者：
Gene Ontology Consortium
DOI：
10.1084/jem.20130731
发表时间：
2013-10-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ge Y;Jiang C;Sung SS;Bagavant H;Dai C;Wang H;Kannapell CC;Cathro HP;Gaskin F;Fu SM
通讯作者：
Fu SM
影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
2.3
作者：
Cutolo, M;Wilder, RL
通讯作者：
Wilder, RL
影响因子：
30.5
作者：
Arazi, Arnon;Rao, Deepak A.;Goldman, Daniel H.
通讯作者：
Goldman, Daniel H.