Tong Jun, Xie Jingyuan, Ren Hong, Liu Jian, Zhang Weijia, Wei Chengguo, Xu Jing, Zhang Wen, Li Xiao, Wang Weiming, Lv Danfeng, He John Cijiang, Chen Nan
Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.
Institute of Nephrology, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.
PLoS One. 2015 Nov 4;10(11):e0140453. doi: 10.1371/journal.pone.0140453. eCollection 2015.
To search for biomarkers to differentiate primary focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD).
We isolated glomeruli from kidney biopsies of 6 patients with adult-onset steroid sensitiveFSGS and 5 patients with MCD, and compared the profiles of glomerular transcriptomes between the two groups of patients using microarray analysis.
Analysis of differential expressed genes (DEGs) revealed that up-regulated DEGs in FSGS patients compared with MCD patients were primarily involved in spermatogenesis, gamete generation, regulation of muscle contraction, response to unfolded protein, cell proliferation and skeletal system development. The down-regulated DEGs were primarily related to metabolic process, intracellular transport, oxidation/reduction andestablishment of intracellular localization. We validated the expression of the top 6 up-regulated and top 6 down-regulated DEGs using real-time PCR. Membrane metallo-endopeptidase (MME) is a down-regulated gene that was previously identified as a key gene for kidney development. Immunostaining confirmed that the protein expression of MME decreased significantly in FSGS kidneys compared with MCD kidneys.
This report was the first study to examine transcriptomes in Chinese patients with various glomerular diseases. Expressions of MME both in RNA and protein level decreased significantly in glomeruli of FSGS kidneys compared with MCD kidneys. Our data suggested that MME might play a role in the normal physiological function of podocytes and a decrease in MME expression might be related to podocyte injury. We also identified genes and pathways specific for FSGS versus MCD, and our data could help identify potential new biomarkers for the differential diagnosis between these two diseases.
寻找可区分原发性局灶节段性肾小球硬化（FSGS）和微小病变肾病（MCD）的生物标志物。
我们从6例成人起病的激素敏感型FSGS患者和5例MCD患者的肾活检组织中分离出肾小球，并用微阵列分析比较两组患者肾小球转录组的特征。
差异表达基因（DEG）分析显示，与MCD患者相比，FSGS患者中上调的DEG主要参与精子发生、配子生成、肌肉收缩调节、未折叠蛋白反应、细胞增殖和骨骼系统发育。下调的DEG主要与代谢过程、细胞内运输、氧化/还原以及细胞内定位的建立有关。我们使用实时PCR验证了上调程度最高的6个DEG和下调程度最高的6个DEG的表达。膜金属内肽酶（MME）是一个下调基因，此前被确定为肾脏发育的关键基因。免疫染色证实，与MCD肾脏相比，FSGS肾脏中MME的蛋白表达显著降低。
本报告是首次对中国各种肾小球疾病患者的转录组进行研究。与MCD肾脏相比，FSGS肾脏肾小球中MME在RNA和蛋白水平的表达均显著降低。我们的数据表明，MME可能在足细胞的正常生理功能中发挥作用，MME表达的降低可能与足细胞损伤有关。我们还确定了FSGS与MCD特有的基因和途径，我们的数据有助于识别这两种疾病鉴别诊断的潜在新生物标志物。
