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尿神经纤毛蛋白-1:狼疮肾炎肾结局的预测性生物标志物。

Urinary Neuropilin-1: A Predictive Biomarker for Renal Outcome in Lupus Nephritis.

机构信息

Hospital Quironsalud del Vallés, Internal Medicine Department, 08202 Sabadell, Spain.

Hospital Universitari Vall d'Hebron, Vall d'Hebron Research Institute (VHIR), Rheumatology research group, Lupus Unit, 08035 Barcelona, Spain.

出版信息

Int J Mol Sci. 2019 Sep 17;20(18):4601. doi: 10.3390/ijms20184601.

Abstract

At present, Lupus Nephritis (LN) is still awaiting a biomarker to better monitor disease activity, guide clinical treatment, and predict a patient's long-term outcome. In the last decade, novel biomarkers have been identified to monitor the disease, but none have been incorporated into clinical practice. The transmembrane receptor neuropilin-1 (NRP-1) is highly expressed by mesangial cells and its genetic deletion results in proteinuric disease and glomerulosclerosis. NRP-1 is increased in kidney biopsies of LN. In this work we were interested in determining whether urinary NRP-1 levels could be a biomarker of clinical response in LN. Our results show that patients with active LN have increased levels of urinary NRP-1. When patients were divided according to clinical response, responders displayed higher urinary and tissue NRP-1 levels at the time of renal biopsy. Areas under the receiver operating characteristic curve, comparing baseline creatinine, proteinuria, urinary NRP-1, and VEGFA protein levels, showed NRP-1 to be an independent predictor for clinical response. In addition, in vitro studies suggest that NRP-1could promote renal recovery through endothelial proliferation and migration, mesangial migration and local T cell cytotoxicity. Based on these results, NRP-1 may be used as an early prognostic biomarker in LN.

摘要

目前,狼疮性肾炎(LN)仍在等待一种生物标志物,以更好地监测疾病活动、指导临床治疗并预测患者的长期预后。在过去十年中,已经确定了一些新的生物标志物来监测该疾病,但没有一种被纳入临床实践。跨膜受体神经纤毛蛋白-1(NRP-1)在系膜细胞中高度表达,其基因缺失会导致蛋白尿疾病和肾小球硬化。在 LN 的肾活检中,NRP-1 增加。在这项工作中,我们有兴趣确定尿 NRP-1 水平是否可以作为 LN 临床反应的生物标志物。我们的结果表明,活动期 LN 患者的尿 NRP-1 水平升高。当根据临床反应对患者进行分组时, responder 患者在肾活检时的尿和组织 NRP-1 水平更高。比较基线肌酐、蛋白尿、尿 NRP-1 和 VEGFA 蛋白水平的受试者工作特征曲线下面积显示,NRP-1 是临床反应的独立预测因子。此外,体外研究表明,NRP-1 可通过内皮细胞增殖和迁移、系膜细胞迁移和局部 T 细胞细胞毒性促进肾脏恢复。基于这些结果,NRP-1 可作为 LN 的早期预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e58d/6769814/d3540f9dfe35/ijms-20-04601-g001.jpg

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