Altered inflammatory and pro-angiogenic responses caused by imbalanced protection against oxidative stress in endometriosis

ABSTRACT: Endometriosis is a common gynecological disease of women in reproductive age, and is primarily thought to arise from retrograde menstruation and implantation of endometrium, mostly into the peritoneal cavity. The condition is characterized by a chronic, unresolved inflammatory process, within which oxidative stress likely plays a critical role. Although elevated reactive oxygen species (ROS) and oxidative stress have previously been postulated as being involved in endometriosis pathogenesis, we set out for a more systematic study to identify novel factors defining oxidative stress in ectopic peritoneal lesions. Using combined proteomic and transcriptomic approaches, we identified novel targets, including upregulated pro-oxidative enzymes such as amine oxidase 3/vascular adhesion protein 1 (AOC3/VAP1), as well as downregulated protective factors such as alkenal reductase PTGR1 or methionine sulfoxide reductase, supporting the observation of increased oxidative protein modification in ectopic lesions and peritoneal fluid. The observed ROS-derived 4-hydroxy-2-nonenal-induced interleukin (IL)-8 release from monocytes indicates a further pathomechanism, whereby elevated IL-8 levels promote further immune cell infiltration and angiogenesis in lesions.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Uterine Endometrium

SUBMITTER: Marie-Laëtitia Thézénas  

LAB HEAD: Professor Benedikt Kessler

PROVIDER: PXD006553 | Pride | 2020-05-26

REPOSITORIES: Pride