Podocytes populate cellular crescents in a murine model of inflammatory glomerulonephritis
Podocytes populate cellular crescents in a murine model of inflammatory glomerulonephritis
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DOI：
10.1097/01.asn.0000102468.37809.c6
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发表时间：
2004-01-01
影响因子：
13.6
通讯作者：
Holzman, LB
中科院分区：
文献类型：
--
作者：
Moeller, MJ;Soofi, A;Holzman, LB
细胞性新月体是许多炎性肾小球肾炎的典型组织学表现。尽管有许多研究，肾小球新月体的起源仍然没有得到解决。用一种新的转基因小鼠模型进行遗传细胞谱系作图研究，以研究内脏肾小球上皮细胞（称为足细胞）是否是细胞新月体的前体细胞。将足细胞特异性2. 5 P-Cre小鼠系与ROSA 26报告细胞系杂交，导致在双转基因2. 5 P-Cre/ROSA 26小鼠中β-半乳糖苷酶的不可逆组成型表达。在这些小鼠中，用先前描述的兔抗肾小球基底膜抗血清肾炎方法诱导新月体肾小球肾炎。有趣的是，来自足细胞的β-半乳糖苷酶阳性细胞粘附在壁基底膜上，并在细胞新月体形成的早期阶段填充肾小球新月体，占总细胞质量的至少四分之一。在细胞新月体中，增殖标记Ki-67在β-半乳糖苷酶阳性和β-半乳糖苷酶阴性细胞中表达，表明两种细胞类型通过原位增殖促进细胞新月体的形成。足细胞特异性抗原，包括WT-1，synaptopodin，nephrin和podocin，在肾小球新月体中的任何细胞都不表达，表明足细胞在该肾炎模型中经历了深刻的表型变化。
Cellular crescents are a defining histologic finding in many forms of inflammatory glomerulonephritis. Despite numerous studies, the origin of glomerular crescents remains unresolved. A genetic cell lineage-mapping study with a novel transgenic mouse model was performed to investigate whether visceral glomerular epithelial cells, termed podocytes, are precursors of cells that populate cellular crescents. The podocyte-specific 2.5P-Cre mouse line was crossed with the ROSA26 reporter line, resulting in irreversible constitutive expression of beta-galactosidase in doubly transgenic 2.5P-Cre/ROSA26 mice. In these mice, crescentic glomerulonephritis was induced with a previously described rabbit anti-glomerular basement membrane antiserum nephritis approach. Interestingly, beta-galactosidase-positive cells derived from podocytes adhered to the parietal basement membrane and populated glomerular crescents during the early phases of cellular crescent formation, accounting for at least one-fourth of the total cell mass. In cellular crescents, the proliferation marker Ki-67 was expressed in beta-galactosidase-positive and beta-galactosidase-negative cells, indicating that both cell types contributed to the formation of cellular crescents through proliferation in situ. Podocyte-specific antigens, including WT-1, synaptopodin, nephrin, and podocin, were not expressed by any cells in glomerular crescents, suggesting that podocytes underwent profound phenotypic changes in this nephritis model.