AEG-1 aggravates inflammation via promoting NALP3 inflammasome formation in murine endometriosis lesions

Abstract

Endometriosis (EMs) is one of the most common gynaecological diseases in women of childbearing age. Astrocyte elevated gene-1 (AEG-1) is associated with the invasion, migration, apoptosis and prognosis of various cancers. However, the roles of AEG-1 in EMs and its corresponding molecular mechanism are still unknown. In this study, animal models of EMs were established and mice were divided into two groups (n = 10): Sham group and EMs group. The EMs cells were isolated from EMs model. The AEG-1 gene was knocked down by shRNA, while the SOCS1 gene was knocked down by siRNA. Histological changes, AEG-1 expression in tissues and inflammatory factors level were detected by H&E staining, immunohistochemistry and ELISA, respectively. RT-qPCR and western blotting were used to determine the expression level of related proteins. The present study found AEG-1 was up-regulated in the EMs model. Enhanced AEG-1 promoted inflammatory cell infiltration, and elevated the levels of IL-1β, IL-6, and TNF-α in EM group (p < 0.05). Besides, AEG-1 overexpression promoted the expression of NALP3, ASC and Cleaved-caspase-1, while decreased SOCS1 level (p < 0.05). Decrease of SOCS1 further promoted the formation of NALP3 inflammasome. The inhibitory effect of AEG-1 on SOCS1 was weakened after the addition of MG-132 (p < 0.01). Furthermore, silencing AEG-1 alone increased SOCS1 level, decreased the levels of inflammatory cytokines, thereby inhibited the formation of NALP3 inflammasome. All these results demonstrated that AEG-1 aggravated inflammation via promoting NALP3 inflammasome formation in murine endometriosis lesions.

Keywords

• endometriosis
• astrocyte elevated gene-1
• inflammation
• nucleotide-binding oligomerization domain-like receptor 3
• suppressor of cytokine signaling1