Proliferating cells in HIV and pamidronate-associated collapsing focal segmental glomerulosclerosis are parietal epithelial cells
Proliferating cells in HIV and pamidronate-associated collapsing focal segmental glomerulosclerosis are parietal epithelial cells
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DOI：
10.1038/sj.ki.5001574
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发表时间：
2006-07-01
影响因子：
19.6
通讯作者：
Wetzels, J. F. M.
中科院分区：
文献类型：
--
作者：
Dijkman, H. B. P. M.;Weening, J. J.;Wetzels, J. F. M.
塌陷性局灶节段性肾小球硬化症（cFSGS）的特征在于肾小球上皮细胞的增生。在FSGS小鼠模型和复发性特发性FSGS患者中，我们将增殖细胞鉴定为壁上皮细胞（佩奇）。在本研究中，我们评估了与人类免疫缺陷病毒（HIV）和帕米膦酸盐相关的cFSGS中增殖细胞的起源。我们对2例HIV相关cFSGS患者的活检和1例帕米膦酸盐相关cFSGS患者的肾切除标本中的肾小球病变进行了详细研究。肾小球进行了研究，连续切片，使用光镜和电子显微镜和免疫组化，以确定上皮细胞表型。我们使用Synaptopodin、血管内皮生长因子和CD 10作为足细胞标记物，CK 8和PAX 2作为PEC标记物，Ki-67作为细胞增殖标记物。新沉积的细胞外基质的特点是使用抗硫酸乙酰肝素单链抗体。增殖细胞的足细胞标志物呈阴性，但染色阳性的PEC标志物和细胞增殖标志物Ki-67。PAX-2和CK 8阳性细胞在毛细血管丛上的增殖与Bowman囊内PAX-2/CK 8阳性细胞的增殖是连续的。由这些增殖细胞沉积的基质与鲍曼氏囊染色相同。我们的研究表明，佩奇在HIV和帕米膦酸盐相关的cFSGS中增殖。我们的数据不支持增殖、去分化足细胞的概念。
Collapsing focal segmental glomerulosclerosis (cFSGS) is characterized by hyperplasia of glomerular epithelial cells. In a mouse model of FSGS and in a patient with recurrent idiopathic FSGS, we identified the proliferating cells as parietal epithelial cells (PECs). In the present study, we have evaluated the origin of the proliferating cells in cFSGS associated with human immunodeficiency virus (HIV) and pamidronate. We performed a detailed study of glomerular lesions in biopsies of two patients with HIV-associated cFSGS and a nephrectomy specimen of a patient with pamidronate-associated cFSGS. Glomeruli were studied by serial sectioning using light and electron microscopy and immunohistochemistry to determine the epithelial cell phenotype. We used Synaptopodin, vascular endothelial growth factor, and CD10 as podocyte markers, CK8 and PAX2 as PEC markers and Ki-67 as marker of cell proliferation. The newly deposited extracellular matrix was characterized using antiheparan sulfate single-chain antibodies. The proliferating cells were negative for the podocyte markers, but stained positive for the PEC markers and the cell proliferation marker Ki-67. The proliferating PAX-2 and CK8 positive cells that covered the capillary tuft were always in continuity with PAX-2/CK8 positive cells lining Bowman's capsule. The matrix deposited by these proliferating cells stained identically to Bowman's capsule. Our study demonstrates that PECs proliferate in HIV and pamidronate-associated cFSGS. Our data do not support the concept of the proliferating, dedifferentiated podocyte.