Identification of a Multi-Messenger RNA Signature as Type 2 Diabetes Mellitus Candidate Genes Involved in Crosstalk between Inflammation and Insulin Resistance

Hebatalla Said Ali; Mariam Sameh Boshra; Sara H. A. Agwa; Mohamed S. Abdel Hakeem; Mahmoud Shawky El Meteini; Marwa Matboli

doi:10.3390/biom12091230

Biomolecules (Sep 2022)

Identification of a Multi-Messenger RNA Signature as Type 2 Diabetes Mellitus Candidate Genes Involved in Crosstalk between Inflammation and Insulin Resistance

Hebatalla Said Ali,
Mariam Sameh Boshra,
Sara H. A. Agwa,
Mohamed S. Abdel Hakeem,
Mahmoud Shawky El Meteini,
Marwa Matboli

Affiliations

Hebatalla Said Ali: Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Abbassia, Cairo P.O. Box 11381, Egypt
Mariam Sameh Boshra: Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Abbassia, Cairo P.O. Box 11381, Egypt
Sara H. A. Agwa: Clinical Pathology, Medical Ain Shams Research Institute, Ain Shams University, Abbassia, Cairo P.O. Box 11381, Egypt
Mohamed S. Abdel Hakeem: Institute of Immunology, University of Pennsylvania, Philadelphia, PA 19014, USA
Mahmoud Shawky El Meteini: Department of General Surgery, The School of Medicine, University of Ain Shams, Cairo 11591, Egypt
Marwa Matboli: Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Ain Shams University, Abbassia, Cairo P.O. Box 11381, Egypt

DOI: https://doi.org/10.3390/biom12091230
Journal volume & issue: Vol. 12, no. 9
p. 1230

Abstract

Read online

Type 2 Diabetes Mellitus (T2DM) is a metabolic disease associated with inflammation widening the scope of immune-metabolism, linking the inflammation to insulin resistance and beta cell dysfunction. New potential and prognostic biomarkers are urgently required to identify individuals at high risk of β-cell dysfunction and pre-DM. The DNA-sensing stimulator of interferon genes (STING) is an important component of innate immune signaling that governs inflammation-mediated T2DM. NOD-like receptor (NLR) reduces STING-dependent innate immune activation in response to cyclic di-GMP and DNA viruses by impeding STING-TBK1 interaction. We proposed exploring novel blood-based mRNA signatures that are selective for components related to inflammatory, immune, and metabolic stress which may reveal the landscape of T2DM progression for diagnosing or treating patients in the pre-DM state. In this study, we used microarray data set to identify a group of differentially expressed mRNAs related to the cGAS/STING, NODlike receptor pathways (NLR) and T2DM. Then, we comparatively analyzed six mRNAs expression levels in healthy individuals, prediabetes (pre-DM) and T2DM patients by real-time PCR. The expressions of ZBP1, DDX58, NFKB1 and CHUK were significantly higher in the pre-DM group compared to either healthy control or T2DM patients. The expression of ZBP1 and NFKB1 mRNA could discriminate between good versus poor glycemic control groups. HSPA1B mRNA showed a significant difference in its expression regarding the insulin resistance. Linear regression analysis revealed that LDLc, HSPA1B and NFKB1 were significant variables for the prediction of pre-DM from the healthy control. Our study shed light on a new finding that addresses the role of ZBP1 and HSPA1B in the early prediction and progression of T2DM.

Published in Biomolecules

ISSN: 2218-273X (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Microbiology
Website: https://www.mdpi.com/journal/biomolecules

About the journal

Abstract

Keywords