{"title":"ECT2 在慢性肾病进展过程中对肾小管间质纤维化的贡献","authors":"Kai-Xin Song, Hua Su","doi":"10.1007/s11596-024-2948-1","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Chronic kidney disease (CKD) is a complex disorder resulting from a combination of various environmental and genetic factors. Considerable efforts have been dedicated to elucidating its etiological mechanisms. Nevertheless, the pathogenic mechanism of CKD remains poorly understood, which hinders the development of effective therapeutic strategies. In this study, we aimed to identify novel mediators that could contribute to the development of CKD.</p><p><strong>Methods: </strong>The ClinVar, STRING, MEME Suite, TRRUST, bedtools, GEO, and R Studio databases and software were used to analyze their common features and investigate potential CKD disease genes. Transcriptomic analysis, immunohistochemistry, qRT-PCR, and Western blotting were utilized to further validate the role of ECT2 in kidney fibrosis.</p><p><strong>Results: </strong>In total, 26 CKD disease genes were obtained from the ClinVar database, and the STRING, MEME Suite, TRRUST, bedtools, and GEO databases and software were used to analyze their common properties and explore potential CKD disease genes. Epithelial cell transforming sequence 2 (ECT2), cyclin B 1, caspase 7 and collagen alpha-1 (IV) were identified as potential candidates for CKD progression. Weighted correlation network analysis (WGCNA) subsequently revealed the relationships between potential genes and CKD. The results of the transcriptomic analysis further confirmed that ECT2 expression was greater in the kidney tissue of CKD patients than in that of healthy controls. Next, immunohistochemistry and Western blotting demonstrated that ECT2 was predominantly expressed in the renal tubules of a unilateral ureteral obstruction (UUO) mouse model. Consistently, in vitro experiments revealed that ECT2 was upregulated in TGF-β1-treated HK-2 cells. Moreover, ECT2 overexpression or knockdown in HK-2 cells altered the intensity of fibrosis markers.</p><p><strong>Conclusion: </strong>ECT2 significantly affects the development and progression of CKD, particularly in association with tubulointerstitial fibrosis.</p>","PeriodicalId":10820,"journal":{"name":"Current Medical Science","volume":" ","pages":"1249-1258"},"PeriodicalIF":2.0000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Contribution of ECT2 to Tubulointerstitial Fibrosis in the Progression of Chronic Kidney Disease.\",\"authors\":\"Kai-Xin Song, Hua Su\",\"doi\":\"10.1007/s11596-024-2948-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>Chronic kidney disease (CKD) is a complex disorder resulting from a combination of various environmental and genetic factors. Considerable efforts have been dedicated to elucidating its etiological mechanisms. Nevertheless, the pathogenic mechanism of CKD remains poorly understood, which hinders the development of effective therapeutic strategies. In this study, we aimed to identify novel mediators that could contribute to the development of CKD.</p><p><strong>Methods: </strong>The ClinVar, STRING, MEME Suite, TRRUST, bedtools, GEO, and R Studio databases and software were used to analyze their common features and investigate potential CKD disease genes. Transcriptomic analysis, immunohistochemistry, qRT-PCR, and Western blotting were utilized to further validate the role of ECT2 in kidney fibrosis.</p><p><strong>Results: </strong>In total, 26 CKD disease genes were obtained from the ClinVar database, and the STRING, MEME Suite, TRRUST, bedtools, and GEO databases and software were used to analyze their common properties and explore potential CKD disease genes. Epithelial cell transforming sequence 2 (ECT2), cyclin B 1, caspase 7 and collagen alpha-1 (IV) were identified as potential candidates for CKD progression. Weighted correlation network analysis (WGCNA) subsequently revealed the relationships between potential genes and CKD. The results of the transcriptomic analysis further confirmed that ECT2 expression was greater in the kidney tissue of CKD patients than in that of healthy controls. Next, immunohistochemistry and Western blotting demonstrated that ECT2 was predominantly expressed in the renal tubules of a unilateral ureteral obstruction (UUO) mouse model. Consistently, in vitro experiments revealed that ECT2 was upregulated in TGF-β1-treated HK-2 cells. Moreover, ECT2 overexpression or knockdown in HK-2 cells altered the intensity of fibrosis markers.</p><p><strong>Conclusion: </strong>ECT2 significantly affects the development and progression of CKD, particularly in association with tubulointerstitial fibrosis.</p>\",\"PeriodicalId\":10820,\"journal\":{\"name\":\"Current Medical Science\",\"volume\":\" \",\"pages\":\"1249-1258\"},\"PeriodicalIF\":2.0000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current Medical Science\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s11596-024-2948-1\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/10/26 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Medical Science","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11596-024-2948-1","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/26 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
摘要
目的：慢性肾脏病（CKD）是一种复杂的疾病，是由各种环境和遗传因素共同作用的结果。人们一直致力于阐明其病因机制。然而，人们对 CKD 的致病机制仍然知之甚少，这阻碍了有效治疗策略的开发。在这项研究中，我们旨在找出可能导致 CKD 发展的新型介质：方法：使用 ClinVar、STRING、MEME Suite、TRRUST、bedtools、GEO 和 R Studio 数据库和软件分析其共同特征并研究潜在的 CKD 疾病基因。利用转录组分析、免疫组化、qRT-PCR和Western印迹技术进一步验证了ECT2在肾脏纤维化中的作用：结果：研究人员从ClinVar数据库中获得了26个CKD疾病基因，并利用STRING、MEME Suite、TRRUST、bedtools和GEO数据库和软件分析了这些基因的共同特性，发掘了潜在的CKD疾病基因。上皮细胞转化序列 2 (ECT2)、细胞周期蛋白 B 1、caspase 7 和胶原蛋白α-1 (IV) 被确定为 CKD 进展的潜在候选基因。随后，加权相关网络分析（WGCNA）揭示了潜在基因与 CKD 之间的关系。转录组分析结果进一步证实，与健康对照组相比，ECT2 在 CKD 患者肾组织中的表达量更高。接着，免疫组化和 Western 印迹显示，ECT2 主要在单侧输尿管梗阻（UUO）小鼠模型的肾小管中表达。与此相一致，体外实验显示，ECT2 在经 TGF-β1 处理的 HK-2 细胞中上调。此外，ECT2在HK-2细胞中的过表达或敲除改变了纤维化标志物的强度：结论：ECT2对CKD的发生和发展有重要影响，尤其是与肾小管间质纤维化有关。
Contribution of ECT2 to Tubulointerstitial Fibrosis in the Progression of Chronic Kidney Disease.
Objective: Chronic kidney disease (CKD) is a complex disorder resulting from a combination of various environmental and genetic factors. Considerable efforts have been dedicated to elucidating its etiological mechanisms. Nevertheless, the pathogenic mechanism of CKD remains poorly understood, which hinders the development of effective therapeutic strategies. In this study, we aimed to identify novel mediators that could contribute to the development of CKD.
Methods: The ClinVar, STRING, MEME Suite, TRRUST, bedtools, GEO, and R Studio databases and software were used to analyze their common features and investigate potential CKD disease genes. Transcriptomic analysis, immunohistochemistry, qRT-PCR, and Western blotting were utilized to further validate the role of ECT2 in kidney fibrosis.
Results: In total, 26 CKD disease genes were obtained from the ClinVar database, and the STRING, MEME Suite, TRRUST, bedtools, and GEO databases and software were used to analyze their common properties and explore potential CKD disease genes. Epithelial cell transforming sequence 2 (ECT2), cyclin B 1, caspase 7 and collagen alpha-1 (IV) were identified as potential candidates for CKD progression. Weighted correlation network analysis (WGCNA) subsequently revealed the relationships between potential genes and CKD. The results of the transcriptomic analysis further confirmed that ECT2 expression was greater in the kidney tissue of CKD patients than in that of healthy controls. Next, immunohistochemistry and Western blotting demonstrated that ECT2 was predominantly expressed in the renal tubules of a unilateral ureteral obstruction (UUO) mouse model. Consistently, in vitro experiments revealed that ECT2 was upregulated in TGF-β1-treated HK-2 cells. Moreover, ECT2 overexpression or knockdown in HK-2 cells altered the intensity of fibrosis markers.
Conclusion: ECT2 significantly affects the development and progression of CKD, particularly in association with tubulointerstitial fibrosis.
期刊介绍：
Current Medical Science provides a forum for peer-reviewed papers in the medical sciences, to promote academic exchange between Chinese researchers and doctors and their foreign counterparts. The journal covers the subjects of biomedicine such as physiology, biochemistry, molecular biology, pharmacology, pathology and pathophysiology, etc., and clinical research, such as surgery, internal medicine, obstetrics and gynecology, pediatrics and otorhinolaryngology etc. The articles appearing in Current Medical Science are mainly in English, with a very small number of its papers in German, to pay tribute to its German founder. This journal is the only medical periodical in Western languages sponsored by an educational institution located in the central part of China.
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