JBRA Assisted Reproduction 2025;29(Suppl.2 SBRA 2025):206
Poster Presentation
29^th Annual Congress of the SBRA. São Paulo/SP - Brazil, 2025
doi: 10.5935/1518-0557.20263879

P-194. Regulation of Pericellular Proteolysis in Human Endometrial Stromal Cells and Its Implications for Endometriosis

Maria Eduarda Leite Simões¹, Stephanie Lins Silveira¹, Amanda Wink Santos¹, Pamela Zanon¹, Letícia Quandt¹, Paula Barros Terraciano¹, Eduardo Pandolfi Passos¹, Markus Berger¹

¹ Grupo de Reprodução e Farmacologia Celular (REPROFARM), Centro de Pesquisa Experimental (CPE), Hospital de Clínicas de Porto Alegre (HCPA) - Porto Alegre - RS - Brasil

Objective: Endometriosis is characterized by the ectopic implantation of endometrial cells, a process that involves cell invasion, extracellular matrix remodeling, and inflammation. This study aimed to evaluate how angiotensin II (Ang II) influences the plasminogen activation system in human endometrial stromal cells (hESCs), and to elucidate the mechanisms through which it modulates cell proliferation, migration, and inflammatory responses.
Methods: Primary hESCs were isolated from patients undergoing IVF procedures and treated in culture with Ang II. Protein expression of components involved in angiotensin and plasminogen-plasmin systems - including tPA, uPA, and uPAR—were assessed. Plasmin activity was measured in cell lysates and conditioned media. Cell viability, proliferation, and migration were evaluated using standard assays. Inflammatory and redox responses were assessed through cytokine profiling and analysis of NADPH oxidase activation. The role of the Ang II receptor AT1R was investigated using pharmacological blockade. All the procedures were approved by the Institutional Ethics Committee (number 2023-0053).
Results: Ang II treatment led to a significant increase in the expression of angiotensin-related precursors, receptors, and converting enzymes in hESCs. Concomitantly, components of the plasminogen activation pathway—tPA, uPA, and uPAR— were upregulated. This upregulation resulted in enhanced plasmin generation on the cell surface and in the extracellular milieu. Elevated plasmin activity correlated with increased degradation of fibrin and matrix proteins, as well as with augmented cell viability, proliferation, and migratory behavior. Migration assays revealed that the pro-migratory effect of Ang II was dependent on active plasmin formation. In parallel, Ang II induced oxidative stress and promoted the expression of proinflammatory cytokines and adhesion molecules, an effect mediated largely by NADPH oxidase. Notably, pharmacological inhibition of AT1R markedly reduced tPA-uPA/uPAR expression, plasmin generation, and hESC migration.
Conclusion: These findings demonstrate that Ang II promotes hESC migration and proliferation by stimulating the plasminogen activation system via the AT1R receptor. The Ang II/AT1R axis orchestrates a pro-invasive, pro-inflammatory phenotype in hESCs through increased plasmin production and redox-inflammatory signaling. Targeting this pathway may represent a novel therapeutic strategy for managing endometriosis.