Bidirectional interaction between PGE₂-preconditioned mesenchymal stem cells and myofibroblasts mediates antifibrotic effects: A proteomic investigation into equine endometrial fibrosis reversal

ABSTRACT: Endometrosis is a prevalent fibrotic condition in mares that impairs reproductive efficiency by inducing transdifferentiation of endometrial stromal cells into myofibroblasts, leading to excessive ECM deposition. Methods: To elucidate the molecular mechanisms underlying fibrosis resolution, this study employed comprehensive proteomic techniques, including LC-MS/MS and SILAC, to analyze the interaction between myofibroblasts and mesenchymal stem cells derived from the endometrium (ET-eMSCs) preconditioned with PGE₂. An in vitro co-culture system was used, with samples collected at baseline and after 48 hours. Results: Proteomic analysis identified significant alterations in proteins associated with ECM remodeling, immune regulation, and cellular stress response. Notably, proteins involved in collagen degradation, antioxidant defense, and growth factor signaling pathways were differentially abundant. Network analyses demonstrated robust interactions among these proteins, suggesting coordinated modulatory effects. The data indicate that PGE₂-primed ET-eMSCs induce a shift in myofibroblast secretory profiles, promoting a reduction in ECM stiffness, tissue reorganization, and activation of resolution pathways. Conclusions: These findings reinforce the therapeutic potential of mesenchymal stem cell-based interventions for fibrotic diseases of the endometrium, opening avenues for regenerative strategies to restore reproductive function in mares.

INSTRUMENT(S):

ORGANISM(S): Equus Caballus (horse)

TISSUE(S): Myofibroblast

SUBMITTER: Guillermo Nourdin  

LAB HEAD: Fidel O. Castro

PROVIDER: PXD067551 | Pride | 2025-09-29

REPOSITORIES: Pride