Tziastoudi Maria, Cholevas Christos, Theoharides Theoharis C, Stefanidis Ioannis
Department of Nephrology, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41500 Larisa, Greece.
First Department of Ophthalmology, Faculty of Health Sciences, Aristotle University of Thessaloniki School of Medicine, AHEPA Hospital, 54636 Thessaloniki, Greece.
Int J Mol Sci. 2021 Dec 21;23(1):20. doi: 10.3390/ijms23010020.
The latest meta-analysis of genome-wide linkage studies (GWLS) identified nine cytogenetic locations suggestive of a linkage with diabetic nephropathy (DN) due to type 1 diabetes mellitus (T1DM) and seven locations due to type 2 diabetes mellitus (T2DM). In order to gain biological insight about the functional role of the genes located in these regions and to prioritize the most significant genetic loci for further research, we conducted a gene ontology analysis with an over representation test for the functional annotation of the protein coding genes. Protein analysis through evolutionary relationships (PANTHER) version 16.0 software and Cytoscape with the relevant plugins were used for the gene ontology analysis, and the overrepresentation test and STRING database were used for the construction of the protein network. The findings of the over-representation test highlight the contribution of immune related molecules like immunoglobulins, cytokines, and chemokines with regard to the most overrepresented protein classes, whereas the most enriched signaling pathways include the VEGF signaling pathway, the Cadherin pathway, the Wnt pathway, the angiogenesis pathway, the p38 MAPK pathway, and the EGF receptor signaling pathway. The common section of T1DM and T2DM results include the significant over representation of immune related molecules, and the Cadherin and Wnt signaling pathways that could constitute potential therapeutic targets for the treatment of DN, irrespective of the type of diabetes.
最新的全基因组连锁研究(GWLS)荟萃分析确定了9个细胞遗传学位置,提示与1型糖尿病(T1DM)所致糖尿病肾病(DN)存在连锁关系,以及7个与2型糖尿病(T2DM)相关的位置。为了深入了解位于这些区域的基因的功能作用,并对最显著的基因位点进行优先级排序以开展进一步研究,我们对蛋白质编码基因的功能注释进行了基因本体分析,并进行了过表达测试。通过进化关系进行蛋白质分析(PANTHER)16.0版软件以及带有相关插件的Cytoscape软件用于基因本体分析,而过表达测试和STRING数据库则用于构建蛋白质网络。过表达测试的结果突出了免疫相关分子(如免疫球蛋白、细胞因子和趋化因子)在最过度表达的蛋白质类别方面的作用,而最富集的信号通路包括血管内皮生长因子(VEGF)信号通路、钙黏蛋白通路、Wnt通路、血管生成通路、p38丝裂原活化蛋白激酶(MAPK)通路和表皮生长因子(EGF)受体信号通路。T1DM和T2DM结果的共同部分包括免疫相关分子的显著过度表达,以及钙黏蛋白和Wnt信号通路,无论糖尿病类型如何,这些通路都可能构成治疗DN的潜在治疗靶点。