The role of extracellular matrix metalloproteinase inducer on the action of dihydrotestosterone against the cellular damage induced by Aβ42

Abstract Clinical studies have revealed that the risk of Alzheimer's disease (AD) in men is increased by age-related androgen depletion. The level of β-amyloid (Aβ) is elevated in the brains of AD patients, and Aβ is believed to play a critical role in the pathology of AD. Some studies have indicated that androgens affect AD risk by regulating the metabolism of Aβ by an unclear mechanism. In this study, we investigated the role of the extracellular matrix metalloproteinase inducer (CD147) in this action. Initially, we demonstrated that androgens positively regulate the expression of CD147 in adult male rats and SH-SY5Y cells. Furthermore, this regulation may involve androgen receptor (AR). Additionally, interference of CD147 expression decreased the clearance of Aβ in culture medium and reduced cell viability. It also affected the morphology of the cells and the expression of apoptosis-related proteins. Finally, we found that interference of CD147 expression blocked the dihydrotestosterone (DHT)-induced reduction in Aβ and the protection of cells. DHT regulates MMP-2's expression through CD147. Together, these results imply that androgen regulation of Aβ and cell protection may be affected by interfering with the expression of CD147.