Integrated Transcriptomic and DNA Methylation Analysis Reveals ITGB2-Mediated Immune Dysregulation in Polycystic Ovary Syndrome and Its Modulation by Rutin.
TL;DR
ITGB2 is associated with inflammatory responses in granulosa cells and may contribute to PCOS-related immune dysregulation via NF-κB activation and Rutin attenuates these inflammatory responses, supporting a potential involvement of the ITGB2/NF-κB axis as a therapeutic target.
Abstract
Objectives
To identify immune-related molecular targets in polycystic ovary syndrome (PCOS) and evaluate the role of integrin beta-2 (ITGB2) and the potential modulation by rutin.
Methods
Follicular fluid cytokines from 30 women with PCOS and 30 control women were profiled. Transcriptomic (GSE34526) and DNA methylation (GSE138573) data were integrated to identify overlapping genes, followed by functional enrichment analyses, protein-protein interaction (PPI), and molecular docking analyses. LPS-stimulated granulosa cells, in the presence or absence of ITGB2 overexpression and rutin treatment, were assessed for gene expression, viability, cytokine secretion, and NF-κB activation.
Results
Women with PCOS had higher IL-5 but lower IL-1β and IL-12p70. ITGB2, ITGAM, and CD86 were upregulated and hypomethylated. Among these, ITGB2 bound rutin with the lowest energy (- 7.8 kcal/mol). Rutin reduced ITGB2 expression, restored viability, suppressed cytokine release, and inhibited NF-κB activation, even under ITGB2 overexpression.
Conclusion
ITGB2 is associated with inflammatory responses in granulosa cells and may contribute to PCOS-related immune dysregulation via NF-κB activation. Rutin attenuates these inflammatory responses, supporting a potential involvement of the ITGB2/NF-κB axis as a therapeutic target. CLINICAL TRIAL NUMBER Not applicable.