SHP2-Triggered Endothelial Cell Activation Fuels Estradiol-Independent Endometrial Sterile Inflammation.

ABSTRACT: Sterile inflammation occurs in various chronic diseases due to many nonmicrobe factors. Examples include endometrial hyperplasia (EH), endometriosis, endometrial cancer, and breast cancer, which are all sterile inflammation diseases induced by estrogen imbalances. However, how estrogen-induced sterile inflammation regulates EH remains unclear. Here, a single-cell RNA-Seq is used to show that SHP2 upregulation in endometrial endothelial cells promotes their inflammatory activation and subsequent transendothelial macrophage migration. Independent of the initial estrogen stimulation, IL1β and TNFα from macrophages then create a feedforward loop that enhances endothelial cell activation and IGF1 secretion. This endothelial cell-macrophage interaction sustains sterile endometrial inflammation a

SUBMITTER: Pan J 

PROVIDER: S-EPMC11538683 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature