CD248+ 基质细胞与进行性慢性肾脏病有关。

CD248+ stromal cells are associated with progressive chronic kidney disease.

机构信息

Institute of Biomedical Research, University of Birmingham, Birmingham, UK.

出版信息

Kidney Int. 2011 Jul;80(2):199-207. doi: 10.1038/ki.2011.103. Epub 2011 Apr 13.

DOI:10.1038/ki.2011.103

Abstract

Stromal fibroblasts are the primary cells of the kidney that produce fibrotic matrix. CD248 is a stromal marker expressed on fibroblasts and pericytes within the human kidney. Here, we tested whether CD248 expression in the kidney colocalizes with fibrosis and if it is associated with known determinants of chronic kidney disease (CKD). CD248 expression was located and quantified in situ by immunohistochemistry in kidney biopsies from 93 patients with IgA nephropathy and compared with 22 archived biopsies encompassing normal kidney tissue as control. In normal kidney tissue, CD248 was expressed by resident pericytes, stromal fibroblasts, and was upregulated in human CKD. The expression was linked to known determinants of renal progression. This relationship was maintained in a multivariate analysis with CD248 expression linked to renal survival. CD248 was expressed by a population of α-smooth muscle actin (SMA)(+) myofibroblasts and α-SMA(-) stromal cells but not expressed on CD45(+) leukocytes. Thus, CD248 defines a subset of stromal cells, including but not limited to some myofibroblasts, linked to albuminuria and tubulointerstitial damage during tissue remodeling in CKD.

摘要

基质成纤维细胞是肾脏的主要细胞，可产生纤维性基质。CD248 是一种基质标志物，在人类肾脏中的成纤维细胞和周细胞上表达。在这里，我们测试了肾脏中 CD248 的表达是否与纤维化共定位，以及它是否与慢性肾脏病 (CKD) 的已知决定因素相关。通过免疫组织化学在 93 例 IgA 肾病患者的肾活检组织中定位和定量检测 CD248 的表达，并与 22 例包含正常肾组织的存档活检组织进行比较作为对照。在正常的肾脏组织中，CD248 由固有周细胞和成纤维细胞表达，并在人类 CKD 中上调。这种表达与已知的肾脏进展决定因素有关。这种相关性在多变量分析中得以维持，其中 CD248 的表达与肾脏存活率相关。CD248 表达于一群 α-平滑肌肌动蛋白 (SMA)(+)肌成纤维细胞和 α-SMA(-)基质细胞，但不表达于 CD45(+)白细胞上。因此，CD248 定义了包括但不限于一些肌成纤维细胞在内的基质细胞亚群，与 CKD 组织重塑过程中的白蛋白尿和肾小管间质损伤有关。