Kidney fibrosis is the common final pathway of chronic kidney disease (CKD), and it is distinguished by inflammation, mesenchymal transition with myofibroblast formation, and epithelial-to-mesenchymal transition (EMT). Macrophages are protuberant inflammatory cells in the kidney, and their roles are dependent on their phenotypes. However, it remains unclear whether tubular epithelial cells (TECs) undergoing EMT can influence the phenotypes of macrophages and the underlying mechanisms during the development of kidney fibrosis. Here, we investigated the characteristics of TECs and macrophages during kidney fibrosis with a focus on EMT and inflammation. We found that the coculture of exosomes from transforming growth factor-beta (TGF-β)-induced TECs with macrophages induced macrophage M1 polarization, while exosomes from TECs without TGF-β stimulation or stimulation with TGF-β alone did not induce an increase in M1 macrophage-related markers. Notably, TECs induced to undergo EMT by TGF-β treatment released more exosomes than the other groups. Furthermore, it is noteworthy that when we injected exosomes from TECs undergoing EMT into mice, in addition to the high level of inflammatory response and the activation of M1 macrophages, the indicators of EMT and renal fibrosis in mouse kidney tissue were correspondingly elevated. In summary, exosomes from TECs undergoing EMT by TGF-β treatment induced M1 polarization and led to a positive feedback effect for further EMT and the development of renal fibrosis. Therefore, the obstacle to the release of such exosomes may be a novel therapeutic strategy for CKD.

目的:分析维持性血液透析(maintenance hemodialysis,MHD)患者透析间歇期时长与主要不良心血管事件(major adverse cardiovascular events,MACE)的关系以及发生MACE的影响因素.方法:MHD患者 89 例,按住院原因分为MACE组(n=36)和非MACE组(n=53),应用多因素Logistic回归分析发生MACE的影响因素,绘制受试者工作特征曲线(receiver operating characteristic curve,ROC),计算曲线下面积(area under curve,AUC),构建预测MHD患者发生MACE的列线图.结果:MHD患者因MACE住院占比 40.45%.MACE组年龄、低密度脂蛋白胆固醇、超敏C反应蛋白、尿酸、B型利钠肽、血清可溶性生长刺激基因表达蛋白 2(growth stimulation expressed gene 2,sST2)水平高于非MACE组,血白蛋白水平低于非MACE组,差异均有统计学意义(P＜0.05).长透析间歇期MHD患者MACE发生率 50.00%.多因素Logistic回归分析显示,长透析间歇期、血尿酸和sST2 水平升高是MHD患者发生MACE的独立危险因素(P＜0.05).ROC曲线分析显示,透析间歇期时长、血尿酸和sST2 水平预测MHD患者发生MACE的AUC分别为0.693、0.711 和0.707.将长透析间歇期、血尿酸和sST2 纳入预测模型,构建预测MHD患者发生MACE的列线图,一致性指数为 0.906.结论:主要不良心血管事件是MHD患者住院的重要原因,长透析间歇期、血尿酸和sST2 水平升高是MHD患者发生MACE的危险因素,长透析间歇期MHD患者易发生MACE.

目的:探讨人骨髓间充质干细胞(human bone marrow mesenchymal stem cells,BM-MSCs)外泌体(exosomes,BM-exo)中微小RNA-93-5P(microRNA-93-5P,miR-93-5P)对小鼠肾脏单侧输尿管梗阻(unilateral ureteral obstruction,UUO)模型的肾脏保护作用及其机制.方法:16只6周龄雄性Balb/c小鼠被分为假手术(Sham)组、UUO+磷酸缓冲盐溶液(phosphate buffered saline,PBS)(UUO模型)组、UUO+BM-exo治疗(BM-exo)组、UUO+BM-exo/miR-93-5P抑制剂(BM-exo/miR-93-5P抑制剂)组,每组4只.在UUO术后的第1、3、5天分别对UUO模型组、BM-exo组和BM-exo/miR-93-5P抑制剂组小鼠尾静脉注射0.1 mL PBS、200μg外泌体和200μg加入miR-93-5P抑制剂的外泌体,UUO术后7 d统一处死小鼠,收集各组小鼠的血清,检测血清肌酐(serum creatinine,Scr)、血尿素氮(blood urea nitrogen,BUN)的表达;留取各组小鼠肾脏组织,采用免疫荧光法验证外泌体在小鼠肾脏内的吞噬情况;HE、过碘酸雪夫(periodic acid-schiff,PAS)和Masson染色法评估肾组织病理学改变;Western Blot法和免疫组化方法检测肾组织中α平滑肌肌动蛋白(αsmooth mus-cle actin,α-SMA)、纤连蛋白(fibronectin,FN)和上皮细胞钙黏蛋白(E-cadherin)的蛋白表达及组织分布情况.结果:与UUO模型组比较,BM-exo组小鼠肾组织病理学改变明显改善;α-SMA、FN、E-cadherin的蛋白表达和组织分布均明显降低,BM-exo/miR-93-5P抑制剂组的变化趋势则与BM-exo组相反.结论:BM-exo通过miR-93-5P介导可显著改善UUO小鼠肾脏的纤维化.

This article analyzes the relationship between cell division cycle (CDC20) molecules and oncology outcomes in patients with renal clear cell carcinoma (KIRC). CDC20 appears to act as a regulatory protein interacting with many other proteins at multiple points in the cycle. The RNA sequencing data and corresponding clinical information of CDC20 molecules were obtained from The Cancer Genome Atlas (TCGA) database. The expression of CDC20 in kidney renal clear cell carcinoma tissue and adjacent normal tissue was detected by immunohistochemical methods. Logistic analysis was performed to analyze the role of CDC20 in the clinicopathological characteristics and prognosis of KIRC. Gene Set Enrichment Analysis (GSEA) was used to identify the signal pathways which were related to CDC20. Independent prognostic factors were evaluated using univariate and multivariate Cox regression analysis. A nomogram involved in CDC20 expression and clinicopathological variables was conducted to predict overall survival (OS) in KIRC patients at 1, 3, and 5 years. Furthermore, the relation between CDC20 and immunity was also studied. Our results showed that CDC20 was upregulated in kidney renal clear cell carcinoma tissues, accompanying shorter OS (all P < 0.05). According to the results obtained by immunohistochemistry and TCGA database, CDC20 was significantly upregulated in kidney renal clear cell carcinoma tissues compared with neighboring normal kidney tissues. Univariate and multivariate Cox regression analysis showed that high expression of CDC20 was an independent prognostic factor of poor prognosis in kidney renal clear cell carcinoma patients (all P < 0.05). GSEA analysis suggested that the high expression of CDC20 was related to eight multiple signaling pathways. In addition, CDC20 was linked to tumour mutation burden (TMB), immune checkpoint molecules, tumour microenvironment, and immunological infiltration.