Characterization of lncRNA and mRNA profiles in rats with diabetic macroangiopathy.

Chan Yang,Qiangfei Yang,Xiaoxu Fu,Min Su,Hong Gao,Chunguang Xie,Lian Du,Wen Zhong,Ran Yan,Xueqin Cai,Ziyan Xie,Laurent Metzinger

doi:10.1371/journal.pone.0243987

Abstract

Diabetic macroangiopathy is part of the most common serious complications of diabetes. Previous studies indicate that lncRNAs involved in the process of diabetes and another vascular disease. However, their detailed mechanism of the lncRNAs involved in diabetic macroangiopathy has not been well characterized. In the present study, we generated rat models of diabetic macroangiopathy induced by High fat of 16weeks. A total of 15 GK rats were constructed as a test group, along with 15 Wistar rats set as control group, and thoracic aorta tissue from each group was collected. Whole genomic RNA sequencing was performed on thoracic aorta tissue; 3223 novel lncRNAs and 20367 annotated lncRNAs were indemnified in thoracic aorta samples, and 864 lncRNAs were expressed differently in the test and control groups. Gene ontology term enrichment showed the apparent enrichment of inflammatory response and cell apoptosis, which consistent with the results of H&E Staining, TUNEL Assay, and ELISA; Extensive literature reveals inflammatory response and cell apoptosis play an important role in the process of diabetic macroangiopathy. The results of the present study indicated that lncRNAs, especially Nrep. bSep08, Col5a1, aSep0, soygee.aSep08-unspliced, NONRATT013247.2, votar.aSep08-unspliced, etc, both participate in and mediate the process of inflammatory response, cell apoptosis. What’s more. Our research provides further insights into understanding of the basic molecular mechanisms underlying diabetic macroangiopathy.

Highlights

The present study showed that disorders of glucose and lipid metabolism, inflammation, oxidative stress, insulin resistance, and apoptosis are closely related to the occurrence and development of diabetic macroangiopathy [2,3,4,5]
Model identification of diabetic macroangiopathy in GK Rat with high fat feeding Our previous study shows that high-fat feeding can successfully induce macrovascular disease in GK rats
While in the test group, H&E staining showed that the inner cell membrane was impaired, the endothelial cells swelled and shed, and there are disordered cells and the reduction of the cell middle membrane and the uneven thickness of the vascular wall (Fig 2B); Besides, The thickness of thoracic aorta was measured, and we found that the thickness of thoracic aorta was significantly decreased in the GK rats of diabetic macroangiopathy (Table 3, Fig 2C)

Summary

Introduction

RNA sequencing identifified the features of lncRNA and mRNA in diabetic macroangiopathy of GK rats We analyzed RNA sequencing (RNA-seq) data from 4 rats randomly selected from each group thoracic aorta samples, in which 61,000,000–82,000,000 raw data and 57,000,000–79,000,000 clean data were obtained (Table 4).

Results

Conclusion