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利用基因组分析探索端粒在糖尿病肾病发病机制和进展中的作用。

Harnessing Genomic Analysis to Explore the Role of Telomeres in the Pathogenesis and Progression of Diabetic Kidney Disease.

机构信息

Centre for Public Health, Queen's University of Belfast, Belfast BT12 6BA, UK.

Regional Nephrology Unit, Belfast City Hospital, Belfast BT9 7AB, UK.

出版信息

Genes (Basel). 2023 Feb 28;14(3):609. doi: 10.3390/genes14030609.

Abstract

The prevalence of diabetes is increasing globally, and this trend is predicted to continue for future decades. Research is needed to uncover new ways to manage diabetes and its co-morbidities. A significant secondary complication of diabetes is kidney disease, which can ultimately result in the need for renal replacement therapy, via dialysis or transplantation. Diabetic kidney disease presents a substantial burden to patients, their families and global healthcare services. This review highlights studies that have harnessed genomic, epigenomic and functional prediction tools to uncover novel genes and pathways associated with DKD that are useful for the identification of therapeutic targets or novel biomarkers for risk stratification. Telomere length regulation is a specific pathway gaining attention recently because of its association with DKD. Researchers are employing both observational and genetics-based studies to identify telomere-related genes associated with kidney function decline in diabetes. Studies have also uncovered novel functions for telomere-related genes beyond the immediate regulation of telomere length, such as transcriptional regulation and inflammation. This review summarises studies that have revealed the potential to harness therapeutics that modulate telomere length, or the associated epigenetic modifications, for the treatment of DKD, to potentially slow renal function decline and reduce the global burden of this disease.

摘要

糖尿病的患病率在全球范围内不断上升,预计这种趋势将在未来几十年持续下去。需要研究新的方法来管理糖尿病及其合并症。糖尿病的一个重要的次要并发症是肾脏疾病,最终可能需要通过透析或移植来进行肾脏替代治疗。糖尿病肾病给患者、他们的家庭和全球医疗保健服务带来了巨大的负担。这篇综述强调了利用基因组、表观基因组和功能预测工具来发现与 DKD 相关的新基因和途径的研究,这些研究有助于确定治疗靶点或用于风险分层的新型生物标志物。端粒长度调节是一个最近受到关注的特定途径,因为它与 DKD 有关。研究人员正在进行观察性和基于遗传学的研究,以确定与糖尿病患者肾功能下降相关的与端粒有关的基因。研究还揭示了端粒相关基因的新功能,超出了端粒长度的直接调节,如转录调节和炎症。这篇综述总结了那些有潜力利用调节端粒长度或相关表观遗传修饰的疗法来治疗 DKD 的研究,以潜在地减缓肾功能下降并减轻这种疾病的全球负担。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f9a/10048490/091fc5451aa9/genes-14-00609-g001.jpg

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