Asialoglycoprotein receptor 1 positively regulates PTGS2-induced inflammatory response in polycystic ovary syndrome via ERK1/2 pathway

Asialoglycoprotein receptor 1 regulates the inflammatory response in granulosa cells associated with polycystic ovary syndrome. In the granulosa cells of individuals with polycystic ovary syndrome, elevated levels of asialoglycoprotein receptor 1 may activate the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway, which in turn enhances the expression of prostaglandin-endoperoxide synthase 2. Abstract This study evaluated whether asialoglycoprotein receptor 1 (ASGR1) can regulate the expression of prostaglandin-endoperoxide synthase 2 (PTGS2) in granulosa cells (GCs) in polycystic ovary syndrome (PCOS). The expression levels of ASGR1 in GCs and PCOS mice ovaries were assessed; to determine the in vivo role of ASGR1, it was overexpressed in the ovaries of female mice via adeno-associated virus injection, and RNA-sequencing analysis revealed that ASGR1 upregulated prostaglandin-endoperoxide synthase 2 (PTGS2). Western blot confirmed the levels of activated ERK1/2 after ASGR1 overexpression, and ERK1/2 agonists and inhibitors were used to validate the downstream effects on PTGS2. Results showed that the expression level of ASGR1 in GCs and ovaries of women and mice with PCOS was significantly elevated. In vitro cell culture results demonstrated that ASGR1 significantly upregulated the ERK1/2 pathway and increased PTGS2 expression in KGN cells. Moreover, through the use of agonists, small interfering RNA, inhibitors, and overexpression strategies, it was identified that the ERK1/2 signaling pathway mediates the ASGR1-induced elevated expression of PTGS2. It was concluded that the agonist effect of ASGR1 on PTGS2 in GCs in PCOS is mediated by the ERK1/2 pathway, and these findings provide new insights into the pathogenesis of PCOS-associated inflammation.