Differential gene expression analysis in 1,25(OH)2D3 treated human monocytes establishes link between AIDS progression, neurodegenerative disorders, and aging

Abstract

Background1,25(OH)2D3 or calcitriol (active form of vitamin D) is a known immunomodulatory vitamin. 1,25(OH)2D3 impacts the regulation of multiple immune cell types including monocytes. Monocytes play important role in regulating viral infections and inflammation. Aberrant regulation of monocytes is associated with various inflammatory disorders including neurological disorders. ObjectivesThe primary objective of this study was to find out the impact of vitamin D in monocytic gene expressions and how it affects disease development and pathogenesis. MethodologyA bioinformatics workflow incorporating pathway analysis using KEGG and GAD disease was employed to collate each set of gene expression data. In Cytoscape, STRING was utilized to determine protein-protein interactions and data analysis. ClueGo was used to show association between diseases. Results1,25(OH)2D3-mediated regulation includes genes associated with transport and surface markers. A significant association of 1,25(OH)2D3 with mitochondrial genes was observed in HIV, Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). We also observed a majority of the shared genes between the neurodegenerative (ND) disorders and HIV, are also associated with aging. From literature review we found out that positively expressed genes upon vitamin D treatment, have a neuroprotective as well as an anti-aging role. ConclusionOverall, the pathway analysis indicates immunomodulatory function of 1,25(OH)2D3 in regulating HIV and neuroinflammation; augments the mitochondrial theory in aging, and suggests a possible neuroprotective and anti-aging role of vitamin D via monocytes.