Bioinformatic analysis of endothelial progenitor cells exposed to folic acid in type 1 diabetes mellitus

Abstract

ABSTRACT. We investigated the effects of type 1 diabetes mellitus (T1DM) on endothelial progenitor cells (EPCs) at the molecular level and assessed the therapeutic potential of folic acid (FA) in DM. We downloaded the gene expression profile of the EPCs from T1DM patients before and after treatment with FA and from healthy controls. We identified the differentially expressed genes (DEGs) in the EPCs from T1DM patients before and after a four-week period of FA treatment and compared them with those obtained from the healthy subjects by using limma package in R language. Then, functional annotation of the DEGs was performed using the online tool Database for Annotation, Visualization and Integrated Discovery (DAVID) based on the Kyoto Encyclopedia of Genes and Genomes database. The expression of 696 genes was altered in the EPCs from T1DM patients compared to those from the healthy controls. These genes were mainly involved in the pathways associated with immune response. FA can normalize majority of the altered gene expression profiles of EPCs from T1DM patients to resemble those of healthy subjects, albeit with some side effects. FA can be a potential therapeutic agent for the treatment of T1DM. However, focused efforts are required to ensure that the dose of FA falls within the permissible pharmacological range.

Specific Role of Impaired Glucose Metabolism and Diabetes Mellitus in Endothelial Progenitor Cell Characteristics and Function

“…92 Moreover, folic acid treatment also shows to normalize the majority of the altered gene expression profiles of EPCs from patients with type 1 DM compared with healthy subjects. 93 In the diabetic mouse model, the overexpression of eNOS in EPCs improves their proangiogenic and antiatherogenic properties. 94 Interestingly, recent studies have suggested that hydrogen sulfide has proangiogenic effects, which improve wound healing via the restoration of EPC functions in diabetic mice.…”

Effects of Folic Acid and Magnesium Co-Administration on Blood Glucose Levels in Streptozotocin—Induced Type I Diabetic Wistar Rats

“…Fang assessed the effect of FA treatment on T1DM by analyzing the gene expression profile of EPCs (Endothelial progenitor cells) from T1DM patients treated with FA and comparing it to that from healthy controls, and showed that FA normalized a majority of changes in gene expression induced by T1DM (99.6%), suggesting the therapeutic potential of FA in the treatment of T1DM [4]. Magnesium is an essential ion involved in glucose homeostasis [12].…”

“…Major contributory factors are hyperglycemia, hypertension, dyslipidemia, overweight, and tobacco use which are amenable to prevention and treatment [2]. The free radical scavenging properties and possible antioxidant activity of folic acid are reported [3,4], assessed the effect of FA treatment on T1DM by analyzing the gene expression profile of EPCs (Endothelial progenitor cells) from T1DM patients treated with FA and comparing it to that from healthy controls, and showed that FA normalized a majority of changes in gene expression induced by T1DM (99.6%), suggesting the therapeutic potential of FA in the treatment of T1DM.…”