Abstract

Non-healing chronic ulcers are a serious complication of diabetes and are a major healthcare problem. While a host of treatments have been explored to heal or prevent these ulcers from forming, these treatments have not been found to be consistently effective in clinical trials. An understanding of the changes in gene expression in the skin of diabetic patients may provide insight into the processes and mechanisms that precede the formation of non-healing ulcers. In this study, we investigated genome wide changes in gene expression in skin between patients with type 2 diabetes and non-diabetic patients using next generation sequencing. We compared the gene expression in skin samples taken from 27 patients (13 with type 2 diabetes and 14 non-diabetic). This information may be useful in identifying the causal factors and potential therapeutic targets for the prevention and treatment of diabetic related diseases.

Highlights

  • Type 2 diabetes affects 29 million people in the U.S, and 170 million people in the world[1]

  • Overall the five most upregulated genes when comparing skin samples from diabetic patients to non-diabetic patients included three non-coding RNA genes (LINC01118, RP11545I5.3 and an unknown long non-coding RNA (lncRNA)), an enzyme involved in lipid metabolism (ABHD16A) and a potassium channel that is important in smooth muscle tone and nerve function (KCNMA1)

  • The most downregulated genes included multiple pseudogenes and lncRNA (LINC01060, HPRT1P2, and CCNYL3) as well as the transcription factor NKX2_1 and a member of the TPD52 protein family associated with proliferation and vesicle trafficking (TPD52L3)

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Summary

Introduction

Type 2 diabetes affects 29 million people in the U.S, and 170 million people in the world[1] This condition can often lead to the disturbance of the blood vessel wall through promotion of vascular inflammation and endothelial cell dysfunction[2, 3]. These abnormalities increase the severity of vascular disease in diabetic patients[4]. Patients with type 2 diabetes are prone to the development of non-healing ulcers, on the lower limbs[5]. These non-healing ulcers are a major factor in the cost of treating diabetes. The majority of these treatments have been found to either be ineffective in clinical trials or have limited benefits in a subset of patients[8]

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