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Defining Biventricular Abnormalities by Cardiac Magnetic Resonance in Pre-Dialysis Patients with Chronic Kidney Disease. 慢性肾脏病透析前患者双心室异常的心脏磁共振诊断。
IF 3.7 4区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2023-02-13 eCollection Date: 2023-08-01 DOI: 10.1159/000529526
Li Qi, Beibei Zhi, Jun Zhang, Lingyan Zhang, Song Luo, Longjiang Zhang

Introduction: The aim of the study was to investigate biventricular structural and functional abnormalities in pre-dialysis patients across stages of chronic kidney disease (CKD) by cardiac magnetic resonance (CMR).

Methods: Fifty-one CKD patients with CMR exams were retrospectively analyzed. Patients were divided into three groups according to estimated glomerular filtration rate (eGFR): CKD 1 group (patients with normal eGFR≥90 mL/min/1.73 m2, n = 20), CKD 2-3 group (patients with eGFR< 90 to ≥30 mL/min/1.73 m2, n = 14), and CKD 4-5 group (patients with eGFR<30 mL/min/1.73 m2, n = 17). Twenty-one age- and sex-matched healthy controls (HC) were recruited. CMR-derived left ventricular (LV) and right ventricular (RV) structural and functional measures were compared. Association between CMR parameters and clinical measures was assessed.

Results: There was an increasing trend in RV mass index (RVMi) and LV mass index (LVMi) with the occurrence and development of CKD from HC group to CKD 4-5 group although no significant difference was observed between CKD 1 group and HC group. LV global radial strain and LV global circumferential strain dropped and native T1 value elevated significantly in CKD 4-5 group compared with the other three groups (all p < 0.05), while RV strain measures, RV ejection fraction, and LV ejection fraction showed no significant difference among 4 groups (all p > 0.05). Elevated LV end-diastolic volume index (β = 0.356, p = 0.016) and RV end-systolic volume index (β = 0.488, p = 0.001) were independently associated with RVMi. Increased systolic blood pressure (β = 0.309, p = 0.004), LV end-systolic volume index (β = 0.633, p < 0.001), and uric acid (β = 0.261, p = 0.013) were independently associated with LVMi. Meanwhile, serum phosphorus (β = 0.519, p = 0.001) was independently associated with native T1 value.

Conclusion: In pre-dialysis CKD patients, left and right ventricular remolding has occurred. RVMi and LVMi were the first changed CMR indexes in the development of CKD when eGFR began to drop. Because fluid volume overload was the independent risk factor for RVMi and LVMi increase, reasonable controlling fluid volume overload may slow down the progression of biventricular remolding and may reduce related cardiovascular disease risk.

引言:本研究的目的是通过心脏磁共振(CMR)研究不同阶段慢性肾脏病(CKD)透析前患者的双心室结构和功能异常。方法:回顾性分析51例进行CMR检查的CKD患者。根据估计的肾小球滤过率(eGFR)将患者分为三组:CKD 1组(eGFR<90至≥30 mL/min/1.73 m2的患者,n=20)、CKD 2-3组(e肾小球滤过率<90至>30 mL/mn/1.73 m2患者,n=14)和CKD 4-5组(eEGFR2患者,n=17)。招募了21名年龄和性别匹配的健康对照(HC)。比较CMR衍生的左心室(LV)和右心室(RV)的结构和功能测量。评估了CMR参数与临床测量之间的相关性。结果:从HC组到CKD 4-5组,RV质量指数(RVMi)和LV质量指数(LVMi)随着CKD的发生和发展有增加的趋势,但CKD 1组和HC组之间没有显著差异。与其他三组相比,CKD 4-5组的左心室整体径向应变和左心室整体周向应变下降,固有T1值显著升高(均p<0.05),而RV应变测量、RV射血分数、,左心室射血分数在4组间无显著性差异(均p>0.05)。左心室舒张末期容积指数(β=0.356,p=0.016)和右心室收缩末期容积指数升高(β=0.488,p=0.001)与RVMi独立相关。收缩压升高(β=0.309,p=0.004)、左心室收缩末期容积指数升高(β0.633,p<0.001)和尿酸升高(β0.261,p=0.013)与LVMi独立相关。同时,血清磷(β=0.519,p=0.001)与天然T1值独立相关。结论:透析前CKD患者发生左、右心室重塑。当eGFR开始下降时,RVMi和LVMi是CKD发展过程中第一个改变的CMR指标。由于液体容量过载是RVMi和LVMi增加的独立风险因素,合理控制液体容量过载可以减缓双心室重塑的进展,并可以降低相关的心血管疾病风险。
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引用次数: 0
Acknowledgement to Reviewers 审稿人致谢
4区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2023-01-01 DOI: 10.1159/000534880
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引用次数: 0
Front & Back Matter 正面和背面
IF 3.7 4区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2023-01-01 DOI: 10.1159/000531309
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引用次数: 0
Contents Vol. 8, 2022 目录2022年第8卷
IF 3.7 4区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2022-11-01 DOI: 10.1159/000528127
Zhi-Hong Liu, Jeffrey B. Kopp
Chunsun Dai – Nanjing Medical University, Nanjing, China Zheng Dong – Augusta University, Augusta, GA, USA Chuan-Ming Hao – Fudan University, Shanghai, China John Cijiang He – Icahn School of Medicine at Mount Sinai, New York, NY, USA Gui-Sen Li – Sichuan Provincial People’s Hospital, Sichuan, China Jing Nie – Southern Medical University, Guangzhou, China Jan Novak – University of Alabama at Birmingham, Birmingham, AL, USA Fan Yi – Shandong University, Jinan, China Shengqiang Yu – Second Military Medical University, Shanghai, China Aihua Zhang – Nanjing Medical University, Nanjing, China Hong Zhang – Peking University, Beijing, China Jinghong Zhao – Third Military Medical University, Chongqing, China
戴春孙-中国南京医科大学-美国奥古斯塔大学,乔治亚州奥古斯塔,美国郝传明-中国复旦大学,上海,美国何次江-伊坎西奈山医学院,纽约,纽约州,美国李桂森-中国四川省人民医院,四川,中国南方医科大学,广州,中国,聂静,Jan Novak -阿拉巴马大学伯明翰分校,美国,易凡,山东大学,济南,余胜强-上海第二军医大学,张爱华-南京医科大学,张宏-北京大学,赵景红-重庆第三军医大学
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引用次数: 1
Extracellular Vesicles That Herald the Scarcity of Oxygen 预示缺氧的细胞外囊泡
IF 3.7 4区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2022-04-22 DOI: 10.1159/000524423
Sekyung Oh, Sang-Ho Kwon
The natural, membrane-bound nanoscale particles, called extracellular vesicles (EVs) have emerged as an effective, versatile vehicle to transport desired drugs specifically to injury sites. Heralding the presence of the scarcity of oxygen, EVs produced from the cells upregulating the expression of the critical transcriptional regulator of hypoxia, HIF-1, can induce a response in ischemia-reperfusion-damaged cells to ameliorate renal tubular injury and inflammation.
被称为细胞外囊泡(EVs)的天然膜结合纳米级颗粒已经成为一种有效的、通用的载体,可以将所需的药物特异性地运输到损伤部位。提示缺氧的存在,由细胞产生的ev上调缺氧的关键转录调节因子HIF-1的表达,可以诱导缺血再灌注损伤细胞的反应,以改善肾小管损伤和炎症。
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引用次数: 0
Venous Thromboembolism in Kidney Diseases and Genetic Predisposition 静脉血栓栓塞在肾脏疾病和遗传易感性
IF 3.7 4区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2022-04-11 DOI: 10.1159/000523777
Tingting Wu, Liang V. Tang, Yu Hu
Background: Many renal diseases have been associated with profound clinical effects on thrombosis. To our knowledge, patients with nephrotic syndrome (NS) and chronic kidney disease (CKD) display an elevated risk of vein thrombosis, which is among the common causes of mortality in patients with renal diseases. In addition, venous thrombosis, as a complication, has also been reported in a variety of other renal diseases such as glomerulonephritis without the NS, hypertensive nephropathy, and polycystic kidney disease. With the increasing incidence of kidney diseases and the deeper understanding of the disease, clinicians are becoming more and more aware of the complications of thrombus formation in kidney disease. Summary: We reviewed recent publications of vein thrombosis in kidney diseases, including primary and secondary glomerular diseases, CKD, hereditary kidney disease, renal transplantation, and hemodialysis-induced, catheter-related thrombus, focusing mainly on the main clinical manifestations, possible mechanisms, related risk factors as well as hereditary influencing factors. Key Messages: Vein thrombosis is a complicated complication of a wide spectrum of kidney diseases due to different possible underlying mechanisms.
背景:许多肾脏疾病与血栓形成有深刻的临床影响。据我们所知,肾病综合征(NS)和慢性肾脏疾病(CKD)患者静脉血栓形成的风险较高,这是肾脏疾病患者死亡的常见原因之一。此外,静脉血栓形成作为一种并发症,在其他多种肾脏疾病中也有报道,如无NS的肾小球肾炎、高血压肾病和多囊肾病。随着肾脏疾病发病率的增加和对疾病认识的加深,临床医生对肾脏疾病血栓形成并发症的认识也越来越高。摘要:我们回顾了近年来在肾脏疾病(包括原发性和继发性肾小球疾病、CKD、遗传性肾脏疾病、肾移植、血液透析诱发的导管相关血栓)中静脉血栓形成的相关文献,重点介绍了静脉血栓形成的主要临床表现、可能的发病机制、相关危险因素以及遗传影响因素。静脉血栓形成是广泛的肾脏疾病的复杂并发症,由于不同的可能的潜在机制。
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引用次数: 4
Acute Kidney Injury Induced by Immune Checkpoint Inhibitors 免疫检查点抑制剂诱导急性肾损伤
IF 3.7 4区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2022-04-04 DOI: 10.1159/000520798
Ruixue Tian, Jin Liang, Rongshan Li, Xiaoshuang Zhou
Background: Recent advances in immune therapy have focused on several agents that target tumor suppression; specifically, use of immune checkpoint inhibitors (ICIs), such as ipilimumab, pembrolizumab, and nivolumab, has become an important strategy in cancer therapy as they improve outcomes in malignant disease. However, the incidence of renal complications arising from the widespread use of ICIs may be underestimated. Summary: The most frequently reported renal condition caused by ICI use is acute interstitial nephritis, and for clinicians, the crucial question is how to effectively manage patients who develop renal side effects due to cancer treatment. Currently, treatment of kidney injury associated with ICIs adheres to clinical guidelines described in Kidney Disease Improving Global Outcomes, which entails drug withdrawal and glucocorticoids or combined immunosuppressant use based on disease stage; however, there is no consensus on renal biopsy. Key Messages: Despite significant progress in prevention and treatment, the incidence and mortality of ICI-induced acute kidney injury (AKI) remain very high. This article will discuss the general clinical manifestations, mechanisms of toxicity, renal complications of ICI therapy, and related biomarkers of renal damage. It is envisaged that this information would help clinicians effectively manage AKI due to ICI therapy.
背景:免疫治疗的最新进展主要集中在几种靶向肿瘤抑制的药物上;特别是,使用免疫检查点抑制剂(ICIs),如ipilimumab, pembrolizumab和nivolumab,已成为癌症治疗的重要策略,因为它们改善了恶性疾病的预后。然而,广泛使用ICIs引起的肾脏并发症的发生率可能被低估了。摘要:急性间质性肾炎是由ICI引起的最常见的肾脏疾病,对于临床医生来说,关键的问题是如何有效地管理因癌症治疗而出现肾脏副作用的患者。目前,与ICIs相关的肾损伤的治疗遵循《肾病改善全球结局》中描述的临床指南,需要根据疾病阶段停药和使用糖皮质激素或联合使用免疫抑制剂;然而,对肾活检没有共识。尽管在预防和治疗方面取得了重大进展,但ici诱导的急性肾损伤(AKI)的发病率和死亡率仍然很高。本文将讨论ICI治疗的一般临床表现、毒性机制、肾脏并发症以及肾脏损害的相关生物标志物。预计这些信息将有助于临床医生有效地管理ICI治疗引起的AKI。
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引用次数: 6
Clinicopathological Spectrum of Cryoglobulinemic Glomerulonephritis without Evidence of Autoimmunity Disorders: A Retrospective Study from a Single Institute of China 无自身免疫性疾病证据的冷球蛋白型肾小球肾炎的临床病理谱:来自中国单一研究所的回顾性研究
IF 3.7 4区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2022-03-25 DOI: 10.1159/000522537
Xin Zhang, Xiao-juan Yu, Chongwen An, Zi-Hao Yong, Su-xia Wang, F. Zhou, Ming-hui Zhao
Background: Cryoglobulinemic glomerulonephritis (Cryo-GN), caused by circulating cryoglobulins, has varied etiology and clinical-pathologic manifestations. This study aimed to investigate the clinicopathological spectrum and outcome of patients with various Cryo-GN in China. Methods: A retrospective review of 74 Chinese patients with biopsy-proven cryoglobulin-related renal lesions in Peking University First Hospital from 2010 to 2020 was performed. Results: The mean age at diagnosis was 52.9 ± 15.0 years, and the female-to-male ratio was about 2/5. For the etiology screening, serum/urine monoclonal immunoglobulin could be detected on immunofixation electrophoresis in 34% of patients, including 6 patients who had hematological malignancies. Fifty-seven percent of patients had HBV infection, far more than HCV infection (5%). Ten percent of patients had other infections, and 27% of patients were classified as essential or idiopathic. Eleven out of the 15 patients with type II cryoglobulinemia had a consistent monotype of serum monoclonal immunoglobulins and monoclonal cryoprecipitate. The clinical manifestations were similar between various types of cryoglobulinemia. Hematuria, proteinuria, hypertension, anemia, and chronic renal insufficiency were the most common features. Fifty-three percent of patients presented with nephrotic syndrome, and 32% experienced acute kidney injury. Hypocomplementemia, serum-positive rheumatoid factor activity, and skin lesions were reported in 45%, 29%, and 28% of patients, respectively. After a median of 24 months follow-up, 18 patients reached end-stage kidney disease. The clone-targeted treatment could retard the renal deterioration compared with immunosuppressive therapy. Conclusions: This was the largest single-center, clinicopathological retrospective study of Cryo-GN in China. Our data strongly support the association between monoclonal gammopathy and type II Cryo-GN. The renal responsive rate of immunosuppressant therapy is still suboptimal. The clone-targeted treatment shows promising effects in patients with type I or II Cryo-GN.
背景:冷球蛋白血症性肾小球肾炎(Cryo-GN)是由循环冷球蛋白引起的,具有多种病因和临床病理表现。本研究旨在探讨中国不同类型Cryo-GN患者的临床病理特征及转归。方法:回顾性分析2010年至2020年北京大学第一医院经活检证实的74例中国患者的低温球蛋白相关性肾脏病变。结果:平均诊断年龄为52.9±15.0岁,男女比例约为2/5。在病因筛查方面,免疫固定电泳可检出34%的患者血清/尿液单克隆免疫球蛋白,其中6例为血液学恶性肿瘤。57%的患者有HBV感染,远高于HCV感染(5%)。10%的患者有其他感染,27%的患者被归类为原发性或特发性。15例II型冷球蛋白血症患者中有11例血清单克隆免疫球蛋白和单克隆冷沉淀的单型一致。不同类型冷球蛋白血症的临床表现相似。血尿、蛋白尿、高血压、贫血和慢性肾功能不全是最常见的特征。53%的患者表现为肾病综合征,32%的患者出现急性肾损伤。缺乏症、血清类风湿因子活性阳性和皮肤病变分别在45%、29%和28%的患者中报告。在平均24个月的随访后,18名患者达到了终末期肾病。与免疫抑制治疗相比,克隆靶向治疗可延缓肾脏恶化。结论:这是中国最大的关于Cryo-GN的单中心临床病理回顾性研究。我们的数据强烈支持单克隆γ病与II型Cryo-GN之间的关联。免疫抑制剂治疗的肾反应率仍不理想。克隆靶向治疗在I型或II型Cryo-GN患者中显示出良好的效果。
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引用次数: 1
Therapeutic Effect of Extracellular Vesicles Derived from HIF Prolyl Hydroxylase Domain Enzyme Inhibitor-Treated Cells on Renal Ischemia/Reperfusion Injury HIF脯氨酸羟化酶结构域酶抑制剂对肾缺血再灌注损伤细胞外泡的治疗作用
IF 3.7 4区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2022-03-25 DOI: 10.1159/000522584
Zhao-ying Ding, T. Tang, Zuo-lin Li, Jingyuan Cao, L. Lv, Yi Wen, Bin Wang, Bi-Cheng Liu
Introduction: Acute kidney injury (AKI) is a major public health problem worldwide. However, there is no definitive therapies to treat established AKI. In this study, we used FG-4592 to induce hypoxia inducible factor (HIF) expression in cells and then explored whether the extracellular vesicles (EVs) secreted by HIF-upregulated cells could alleviate ischemia/reperfusion injury (IRI)-induced AKI. Methods: FG-4592/HK2-EVs and FG-4592/HEK293-EVs were prepared by treating HK2 or HEK293 cells with FG-4592 for 24 h, respectively. HK2 cells under hypoxia were treated with FG-4592/HK2-EVs or FG-4592/HEK293-EVs to observe the therapeutic effect of EVs on H/R-induced apoptosis and inflammation. Mice were treated with FG-4592/HEK293-EVs after IRI to observe whether FG-4592/HEK293-EVs treatment could alleviate ischemic AKI. Results: The expression of HIF was induced by FG-4592 in a dose-dependent manner in HK2 and HEK293 cells under normoxia. In vitro, FG-4592/HK2-EVs and FG-4592/HEK293-EVs inhibited apoptosis and inflammation induced by H/R. In vivo, treatment with FG-4592/HEK293-EVs significantly ameliorated renal tubular injury and inflammation caused by IRI. In addition, the expression of HIF-1α in cells and kidneys was significantly downregulated by FG-4592/HK2-EVs and FG-4592/HEK293-EVs treatment. Conclusion: This study demonstrated that EVs derived from HK2 or HEK293 cells after FG-4592 treatment could alleviate renal tubular injury and inflammation, suggesting a novel therapeutic role of FG-4592/EVs in the treatment of AKI.
急性肾损伤(AKI)是世界范围内主要的公共卫生问题。然而,目前还没有明确的治疗方法来治疗已确定的AKI。本研究通过FG-4592诱导细胞缺氧诱导因子(hypoxia inducible factor, HIF)表达,探讨HIF上调的细胞分泌的细胞外囊泡(extracellular vesicles, EVs)是否能减轻缺血再灌注损伤(ischemia/reperfusion injury, IRI)诱导的AKI。方法:FG-4592分别作用于HK2和HEK293细胞24 h,制备FG-4592/HK2- ev和FG-4592/HEK293- ev。用FG-4592/HK2- ev或FG-4592/ hek293 - ev处理缺氧状态下的HK2细胞,观察ev对H/ r诱导的细胞凋亡和炎症的治疗作用。小鼠IRI后给予FG-4592/ hek293 - ev,观察FG-4592/ hek293 - ev是否能缓解缺血性AKI。结果:FG-4592在常氧条件下诱导HK2和HEK293细胞中HIF的表达呈剂量依赖性。在体外,FG-4592/ hk2 - ev和FG-4592/ hek293 - ev可抑制H/R诱导的细胞凋亡和炎症。在体内,FG-4592/ hek293 - ev治疗可显著改善IRI引起的肾小管损伤和炎症。此外,FG-4592/ hk2 - ev和FG-4592/ hek293 - ev可显著下调细胞和肾脏中HIF-1α的表达。结论:本研究表明FG-4592治疗后,来自HK2或HEK293细胞的ev可减轻肾小管损伤和炎症,提示FG-4592/ ev在AKI治疗中具有新的治疗作用。
{"title":"Therapeutic Effect of Extracellular Vesicles Derived from HIF Prolyl Hydroxylase Domain Enzyme Inhibitor-Treated Cells on Renal Ischemia/Reperfusion Injury","authors":"Zhao-ying Ding, T. Tang, Zuo-lin Li, Jingyuan Cao, L. Lv, Yi Wen, Bin Wang, Bi-Cheng Liu","doi":"10.1159/000522584","DOIUrl":"https://doi.org/10.1159/000522584","url":null,"abstract":"Introduction: Acute kidney injury (AKI) is a major public health problem worldwide. However, there is no definitive therapies to treat established AKI. In this study, we used FG-4592 to induce hypoxia inducible factor (HIF) expression in cells and then explored whether the extracellular vesicles (EVs) secreted by HIF-upregulated cells could alleviate ischemia/reperfusion injury (IRI)-induced AKI. Methods: FG-4592/HK2-EVs and FG-4592/HEK293-EVs were prepared by treating HK2 or HEK293 cells with FG-4592 for 24 h, respectively. HK2 cells under hypoxia were treated with FG-4592/HK2-EVs or FG-4592/HEK293-EVs to observe the therapeutic effect of EVs on H/R-induced apoptosis and inflammation. Mice were treated with FG-4592/HEK293-EVs after IRI to observe whether FG-4592/HEK293-EVs treatment could alleviate ischemic AKI. Results: The expression of HIF was induced by FG-4592 in a dose-dependent manner in HK2 and HEK293 cells under normoxia. In vitro, FG-4592/HK2-EVs and FG-4592/HEK293-EVs inhibited apoptosis and inflammation induced by H/R. In vivo, treatment with FG-4592/HEK293-EVs significantly ameliorated renal tubular injury and inflammation caused by IRI. In addition, the expression of HIF-1α in cells and kidneys was significantly downregulated by FG-4592/HK2-EVs and FG-4592/HEK293-EVs treatment. Conclusion: This study demonstrated that EVs derived from HK2 or HEK293 cells after FG-4592 treatment could alleviate renal tubular injury and inflammation, suggesting a novel therapeutic role of FG-4592/EVs in the treatment of AKI.","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"134 1","pages":"206 - 216"},"PeriodicalIF":3.7,"publicationDate":"2022-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77393273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 6
Long Noncoding RNA MEG3-205/Let-7a/MyD88 Axis Promotes Renal Inflammation and Fibrosis in Diabetic Nephropathy 长链非编码RNA MEG3-205/Let-7a/MyD88轴促进糖尿病肾病的肾脏炎症和纤维化
IF 3.7 4区 医学 Q1 UROLOGY & NEPHROLOGY Pub Date : 2022-03-17 DOI: 10.1159/000523847
Q. Luo, X. Xia, Q. Luo, Y. Qiu, Lan Dong, Chen Zhao, F. Peng, Jing Yu, F. Huang, F. He
Aim: The aim of this study was to investigate the role and mechanism of long noncoding RNA (lncRNA) maternally expressed gene 3 (MEG3)-205 in renal inflammation and fibrosis in diabetic nephropathy (DN). Materials and Methods: lncRNA microarray profiling was used to examine differentially expressed lncRNAs of kidney tissues in db/db mice compared to db/m mice. Mouse mesangial cells (mMCs) were cultured in vitro with advanced glycation end products (AGEs) via transfection with lncRNA MEG3-205 siRNAs or plasmids. The role of lncRNA MEG3-205 in vivo was examined in db/db mice treated with long-acting lncRNA MEG3-205 siRNA. The interaction between lncRNA MEG3-205 and let-7a was investigated using luciferase assay and RNA immunoprecipitation assay. Results: lncRNA MEG3-205 was markedly upregulated in renal tissues of db/db mice, DN patients, and AGEs-treated mesangial cells. Overexpression of lncRNA MEG3-205 promoted the secretion of pro-inflammatory cytokines and synthesis of extracellular matrix proteins in mesangial cells. Both lncRNA MEG3-205 and myeloid differentiation primary-response protein 88 (MyD88) could bind to let-7a, and lncRNA MEG3-205 overexpression can significantly rescue the silencing effect of let-7a on MyD88 protein expression in mMCs. Mechanistically, we identified that lncRNA MEG3-205 could act as a competing endogenous RNA by binding with let-7a and thus regulate MyD88. Knockdown of lncRNA MEG3-205 alleviated albuminuria and attenuated renal inflammation and fibrosis in db/db mice. Conclusion: These findings indicated an important role of the lncRNA MEG3-205/let-7a/MyD88 axis in regulating renal inflammation and fibrosis in DN. Targeting lncRNA MEG3-205 might present a promising therapeutic strategy for DN.
目的:本研究旨在探讨长链非编码RNA (lncRNA)母系表达基因3 (MEG3)-205在糖尿病肾病(DN)肾脏炎症和纤维化中的作用及机制。材料和方法:采用lncRNA微阵列分析方法检测db/db小鼠与db/m小鼠肾脏组织中lncRNA的差异表达。通过转染lncRNA MEG3-205 sirna或质粒,用晚期糖基化终产物(AGEs)体外培养小鼠系膜细胞(mmc)。在用长效lncRNA MEG3-205 siRNA处理的db/db小鼠中,研究了lncRNA MEG3-205在体内的作用。采用荧光素酶法和RNA免疫沉淀法研究lncRNA MEG3-205与let-7a的相互作用。结果:lncRNA MEG3-205在db/db小鼠、DN患者和ages处理的肾系膜细胞的肾组织中显著上调。lncRNA MEG3-205的过表达促进了系膜细胞促炎细胞因子的分泌和细胞外基质蛋白的合成。lncRNA MEG3-205和髓样分化初级反应蛋白88 (MyD88)均可与let-7a结合,且lncRNA MEG3-205过表达可显著恢复let-7a对mmc中MyD88蛋白表达的沉默作用。在机制上,我们发现lncRNA MEG3-205可以通过与let-7a结合而作为竞争性内源性RNA,从而调节MyD88。lncRNA MEG3-205的敲低可减轻db/db小鼠的蛋白尿,减轻肾脏炎症和纤维化。结论:这些发现提示lncRNA MEG3-205/let-7a/MyD88轴在调节DN患者肾脏炎症和纤维化中发挥重要作用。靶向lncRNA MEG3-205可能是一种很有前景的DN治疗策略。
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引用次数: 5
期刊
Kidney Diseases
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