Riddhi G Agarwal, Manoj Khokhar, Purvi Purohit, Anupama Modi, Nitin K Bajpai, Gopal K Bohra, Mahendra K Garg, Praveen Sharma
{"title":"microRNA-21和生长分化因子-15在糖尿病前期、2型糖尿病和糖尿病肾病中的表达的临床和计算机研究","authors":"Riddhi G Agarwal, Manoj Khokhar, Purvi Purohit, Anupama Modi, Nitin K Bajpai, Gopal K Bohra, Mahendra K Garg, Praveen Sharma","doi":"10.23736/S2724-6507.22.03646-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Diabetic nephropathy (DN), a microvascular complication associated with long-standing diabetes, is a major cause of the end-stage renal disease (ESRD). Our in-silico analysis indicates several enrichment analyses involved in glucose metabolism to be affected by GDF15 transcription factors.</p><p><strong>Methods: </strong>In-silico analysis was used to identify GDF15 and Insulin related protein-protein interaction (PPI) network and a common set of GDF15 regulating transcription factors by various databases. Common targeting miRNA of GDF15 regulating transcription factors were investigated in miRNet and TargetScan. Further, healthy controls (N.=30) and patients with pre-type-2 diabetes mellitus (pre-diabetes) (N.=30), T2DM (N.=30) and DN (N.=30) were included for analysis of routine biochemical tests, serum GDF15 levels by ELISA and to evaluate the Fold change expression (FCE) of circulating hsa-miR-21 by RT-PCR.</p><p><strong>Results: </strong>MicroRNA-21 was found to directly target GDF15 downregulating transcription factors KLF4, TP53, and CEBPB. A significant difference in the levels of serum GDF15 was observed in Pre-diabetes (708.56±76.37), T2DM (1528.87±140.75) and DN patients (10-fold higher; 5507.90±503.88) when compared to healthy controls (567.36±69.99). The FCE of circulating hsa-miR-21 was 6.19 (pre-diabetes), 8.22 (T2DM), 9.19 (DN), folds higher in cases as compared to controls, reflecting an increasing trend and several folds higher levels of hsa-miR-21 in patients.</p><p><strong>Conclusions: </strong>We suggest the potential of serum GDF15 and circulating-hsa-miR-21 to serve as clinically important biomarkers and therapeutic targets for controlling advancement of diabetes to DN.</p>","PeriodicalId":18690,"journal":{"name":"Minerva endocrinology","volume":"48 2","pages":"172-185"},"PeriodicalIF":2.5000,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"4","resultStr":"{\"title\":\"A clinical and in-silico study of microRNA-21 and growth differentiation factor-15 expression in pre-diabetes, type 2 diabetes and diabetic nephropathy.\",\"authors\":\"Riddhi G Agarwal, Manoj Khokhar, Purvi Purohit, Anupama Modi, Nitin K Bajpai, Gopal K Bohra, Mahendra K Garg, Praveen Sharma\",\"doi\":\"10.23736/S2724-6507.22.03646-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Diabetic nephropathy (DN), a microvascular complication associated with long-standing diabetes, is a major cause of the end-stage renal disease (ESRD). Our in-silico analysis indicates several enrichment analyses involved in glucose metabolism to be affected by GDF15 transcription factors.</p><p><strong>Methods: </strong>In-silico analysis was used to identify GDF15 and Insulin related protein-protein interaction (PPI) network and a common set of GDF15 regulating transcription factors by various databases. Common targeting miRNA of GDF15 regulating transcription factors were investigated in miRNet and TargetScan. Further, healthy controls (N.=30) and patients with pre-type-2 diabetes mellitus (pre-diabetes) (N.=30), T2DM (N.=30) and DN (N.=30) were included for analysis of routine biochemical tests, serum GDF15 levels by ELISA and to evaluate the Fold change expression (FCE) of circulating hsa-miR-21 by RT-PCR.</p><p><strong>Results: </strong>MicroRNA-21 was found to directly target GDF15 downregulating transcription factors KLF4, TP53, and CEBPB. A significant difference in the levels of serum GDF15 was observed in Pre-diabetes (708.56±76.37), T2DM (1528.87±140.75) and DN patients (10-fold higher; 5507.90±503.88) when compared to healthy controls (567.36±69.99). 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引用次数: 4
摘要
背景:糖尿病肾病(DN)是一种与长期糖尿病相关的微血管并发症,是终末期肾脏疾病(ESRD)的主要原因。我们的计算机分析表明,GDF15转录因子会影响葡萄糖代谢的一些富集分析。方法:采用计算机分析方法,通过多种数据库鉴定GDF15与胰岛素相关蛋白-蛋白相互作用(Insulin related protein-protein interaction, PPI)网络和一组通用的GDF15调节转录因子。在miRNet和TargetScan中研究了GDF15调控转录因子的常见靶向miRNA。选取健康对照(n =30)、2型糖尿病前期(n =30)、2型糖尿病前期(n =30)、DN患者(n =30)进行常规生化检测、ELISA检测血清GDF15水平,RT-PCR检测循环hsa-miR-21的Fold change expression (FCE)。结果:发现MicroRNA-21直接靶向GDF15下调转录因子KLF4、TP53、CEBPB。糖尿病前期(708.56±76.37)、T2DM(1528.87±140.75)和DN患者血清GDF15水平差异有统计学意义(高10倍;5507.90±503.88),而健康对照组(567.36±69.99)。循环hsa-miR-21的FCE为6.19(糖尿病前期),8.22 (T2DM), 9.19 (DN),与对照组相比,病例中hsa-miR-21的FCE增加了几倍,反映了患者中hsa-miR-21水平的增加趋势。结论:我们认为血清GDF15和circular -hsa- mir -21可能是控制糖尿病向DN进展的重要临床生物标志物和治疗靶点。
A clinical and in-silico study of microRNA-21 and growth differentiation factor-15 expression in pre-diabetes, type 2 diabetes and diabetic nephropathy.
Background: Diabetic nephropathy (DN), a microvascular complication associated with long-standing diabetes, is a major cause of the end-stage renal disease (ESRD). Our in-silico analysis indicates several enrichment analyses involved in glucose metabolism to be affected by GDF15 transcription factors.
Methods: In-silico analysis was used to identify GDF15 and Insulin related protein-protein interaction (PPI) network and a common set of GDF15 regulating transcription factors by various databases. Common targeting miRNA of GDF15 regulating transcription factors were investigated in miRNet and TargetScan. Further, healthy controls (N.=30) and patients with pre-type-2 diabetes mellitus (pre-diabetes) (N.=30), T2DM (N.=30) and DN (N.=30) were included for analysis of routine biochemical tests, serum GDF15 levels by ELISA and to evaluate the Fold change expression (FCE) of circulating hsa-miR-21 by RT-PCR.
Results: MicroRNA-21 was found to directly target GDF15 downregulating transcription factors KLF4, TP53, and CEBPB. A significant difference in the levels of serum GDF15 was observed in Pre-diabetes (708.56±76.37), T2DM (1528.87±140.75) and DN patients (10-fold higher; 5507.90±503.88) when compared to healthy controls (567.36±69.99). The FCE of circulating hsa-miR-21 was 6.19 (pre-diabetes), 8.22 (T2DM), 9.19 (DN), folds higher in cases as compared to controls, reflecting an increasing trend and several folds higher levels of hsa-miR-21 in patients.
Conclusions: We suggest the potential of serum GDF15 and circulating-hsa-miR-21 to serve as clinically important biomarkers and therapeutic targets for controlling advancement of diabetes to DN.