PAI1 regulating CHRNA1 contributes to primary focal hyperhidrosis: Clinical and experimental studies

Primary focal hyperhidrosis (PFH) is a debilitating condition characterized by localized excessive sweating, yet its underlying mechanisms remain poorly understood. In this study, sweat gland tissues from PFH patients (n = 204) and healthy controls (n = 60) were analyzed to assess the mRNA and protein levels of plasminogen activator inhibitor 1 (PAI-1) and nicotinic acetylcholine receptor alpha 1 subunit (CHRNA1) using RT-qPCR and western blotting. Primary sweat gland cells were isolated for in vitro experiments, and a pilocarpine-induced hyperhidrosis mouse model was established to evaluate the therapeutic effect of recombinant human PAI-1 (rhPAI-1). PFH patients showed significantly reduced PAI-1 expression and elevated CHRNA1 expression compared to controls (p < 0.01). Treatment with rhPAI-1 downregulated CHRNA1 and aquaporin 5 (AQP5) expression in sweat gland cells and decreased sweat secretion and serum acetylcholine levels in vivo. These results suggest that PAI-1 negatively regulates CHRNA1 and AQP5 expression, offering new insights into the molecular pathology of PFH and identifying PAI-1 as a potential therapeutic target for hyperhidrosis.