Mechanistic exploration of bisphenol A in primary Sjögren's syndrome using network toxicology, molecular docking,...

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disorder marked by exocrine gland impairment and systemic manifestations. Environmental endocrine disruptors, including bisphenol A (BPA), have been associated with immunological dysregulation; however, their involvement in pSS is not well-defined. This study integrated network toxicology, molecular docking, molecular dynamics simulation, and in vitro validation to examine the potential effects of BPA on pSS. Bioinformatics investigation revealed 25 overlapping targets between BPA-associated genes and differentially expressed genes related to pSS, with CASP3, PTGS1, and PTGS2 identified as main possibilities. Molecular docking and molecular dynamics simulations validated robust and stable interactions of BPA with these proteins. Cellular studies with human submandibular gland epithelial cells demonstrated dose-dependent cytotoxicity of BPA, accompanied by substantial overexpression of CASP3, PTGS1, and PTGS2 at 1 µM exposure. The data indicate that BPA enhances apoptosis and inflammatory signaling in salivary gland cells, potentially contributing to pSS progression. This study provides mechanistic insight into how BPA may contribute to autoimmune disease development, highlighting its potential role in pSS.