Smeets Bart, Uhlig Sandra, Fuss Astrid, Mooren Fieke, Wetzels Jack F M, Floege Jürgen, Moeller Marcus J
Department of Nephrology and Immunology, University Hospital of the Aachen University of Technology, Pauwelsstrasse 30, Aachen, Germany.
J Am Soc Nephrol. 2009 Dec;20(12):2604-15. doi: 10.1681/ASN.2009010122. Epub 2009 Nov 16.
Cellular lesions form in Bowman's space in both crescentic glomerulonephritis and collapsing glomerulopathy. The pathomechanism and origin of the proliferating cells in these lesions are unknown. In this study, we examined proliferating cells by lineage tracing of either podocytes or parietal epithelial cells (PECs) in the nephrotoxic nephritis model of inflammatory crescentic glomerulonephritis. In addition, we traced the fate of genetically labeled PECs in the Thy-1.1 transgenic mouse model of collapsing glomerulopathy. In both models, cellular bridges composed of PECs were observed between Bowman's capsule and the glomerular tuft. Genetically labeled PECs also populated larger, more advanced cellular lesions. In these lesions, we detected de novo expression of CD44 in activated PECs. In contrast, we rarely identified genetically labeled podocytes within the cellular lesions of crescentic glomerulonephritis. In conclusion, PECs constitute the majority of cells that compose early extracapillary proliferative lesions in both crescentic glomerulonephritis and collapsing glomerulopathy, suggesting similar pathomechanisms in both diseases.
在新月体性肾小球肾炎和塌陷性肾小球病中，细胞性病变均在鲍曼间隙形成。这些病变中增殖细胞的发病机制和来源尚不清楚。在本研究中，我们通过在炎性新月体性肾小球肾炎的肾毒性肾炎模型中对足细胞或壁层上皮细胞（PEC）进行谱系追踪来检测增殖细胞。此外，我们在塌陷性肾小球病的Thy-1.1转基因小鼠模型中追踪了基因标记的PEC的命运。在这两种模型中，均观察到在鲍曼囊和肾小球毛细血管襻之间存在由PEC组成的细胞桥。基因标记的PEC也聚集在更大、更进展的细胞性病变中。在这些病变中，我们在活化的PEC中检测到CD44的从头表达。相比之下，在新月体性肾小球肾炎的细胞性病变中，我们很少鉴定出基因标记的足细胞。总之，PEC构成了新月体性肾小球肾炎和塌陷性肾小球病中早期毛细血管外增殖性病变的大多数细胞，提示这两种疾病具有相似的发病机制。
