4.7 Review

Emerging Role of Long Non-Coding RNAs in Diabetic Vascular Complications

Journal

FRONTIERS IN ENDOCRINOLOGY
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fendo.2021.665811

Keywords

diabetes; diabetes complications; long non-coding RNAs; inflammation; fibrosis; epigenetics

Funding

  1. National Institutes of Health (NIDDK)
  2. National Institutes of Health (NHLBI) [R01 DK065073, R01 HL106089, R01 DK081705, DP3 DK106917]
  3. Schaeffer Foundation
  4. Wanek Family Project for the Cure of Type 1 Diabetes at City of Hope

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Chronic metabolic disorders like obesity and diabetes are associated with accelerated vascular complications, and long non-coding RNAs play a crucial role in regulating gene expression in these diseases. Understanding the characteristics and mechanisms of lncRNAs can provide insights for the development of new therapeutic approaches to manage these disorders effectively.
Chronic metabolic disorders such as obesity and diabetes are associated with accelerated rates of macrovascular and microvascular complications, which are leading causes of morbidity and mortality worldwide. Further understanding of the underlying molecular mechanisms can aid in the development of novel drug targets and therapies to manage these disorders more effectively. Long non-coding RNAs (lncRNAs) that do not have protein-coding potential are expressed in a tissue- and species-specific manner and regulate diverse biological processes. LncRNAs regulate gene expression in cis or in trans through various mechanisms, including interaction with chromatin-modifying proteins and other regulatory proteins and via posttranscriptional mechanisms, including acting as microRNA sponges or as host genes of microRNAs. Emerging evidence suggests that major pathological factors associated with diabetes such as high glucose, free fatty acids, proinflammatory cytokines, and growth factors can dysregulate lncRNAs in inflammatory, cardiac, vascular, and renal cells leading to altered expression of key inflammatory genes and fibrotic genes associated with diabetic vascular complications. Here we review recent reports on lncRNA characterization, functions, and mechanisms of action in diabetic vascular complications and translational approaches to target them. These advances can provide new insights into the lncRNA-dependent actions and mechanisms underlying diabetic vascular complications and uncover novel lncRNA-based biomarkers and therapies to reduce disease burden and mortality.

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