Transcript Expression Profiles and MicroRNA Regulation Indicate an Upregulation of Processes Linked to Oxidative Stress, DNA Repair, Cell Death, and Inflammation in Type 1 Diabetes Mellitus Patients

Author(s)

Takahashi, Paula ; Xavier, Danilo J. ; Lima, Jessica E. B. F. ; Evangelista, Adriane F. ; Collares, Cristhianna V. A. ; Foss-Freitas, Maria C. ; Rassi, Diane M. ; Donadi, Eduardo A. ; Passos, Geraldo A. ; Sakamoto-Hojo, Elza T.

• Document type: Journal article
• Source: JOURNAL OF DIABETES RESEARCH; v. 2022, p. 15-pg., 2022-02-01.

Abstract

Type 1 diabetes (T1D) arises from autoimmune-mediated destruction of insulin-producing beta-cells leading to impaired insulin secretion and hyperglycemia. T1D is accompanied by DNA damage, oxidative stress, and inflammation, although there is still scarce information about the oxidative stress response and DNA repair in T1D pathogenesis. We used the microarray method to assess mRNA expression profiles in peripheral blood mononuclear cells (PBMCs) of 19 T1D patients compared to 11 controls and identify mRNA targets of microRNAs that were previously reported for T1D patients. We found 277 differentially expressed genes (220 upregulated and 57 downregulated) in T1D patients compared to controls. Analysis by gene sets (GSA and GSEA) showed an upregulation of processes linked to ROS generation, oxidative stress, inflammation, cell death, ER stress, and DNA repair in T1D patients. Besides, genes related to oxidative stress responses and DNA repair (PTGS2, ATF3, FOSB, DUSP1, and TNFAIP3) were found to be targets of four microRNAs (hsa-miR-101, hsa-miR148a, hsa-miR-27b, and hsa-miR-424). The expression levels of these mRNAs and microRNAs were confirmed by qRT-PCR. Therefore, the present study on differential expression profiles indicates relevant biological functions related to oxidative stress response, DNA repair, inflammation, and apoptosis in PBMCs of T1D patients relative to controls. We also report new insights regarding microRNA-mRNA interactions, which may play important roles in the T1D pathogenesis. (AU)

• FAPESP's process: 08/56594-8 - Control of the transcriptome in diabetes mellitus
• Grantee: Geraldo Aleixo da Silva Passos Júnior
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/09352-7 - Genomic instability and molecular signaling pathways involving DNA damage responses and DNA repair in human diseases
• Grantee: Elza Tiemi Sakamoto Hojo
• Support Opportunities: Regular Research Grants
• FAPESP's process: 10/12069-7 - Gene expression profiles and possible interactions between microRNAs and mRNAs in type 1 Diabetes Mellitus, focusing on response to oxidative stress and DNA repair
• Grantee: Paula Takahashi
• Support Opportunities: Scholarships in Brazil - Doctorate