Targeting galectin-1-induced angiogenesis mitigates the severity of endometriosis.

Endometriosis is characterized by the presence of endometrial tissue outside the uterus that causes severe pelvic pain and infertility in women of reproductive age. Although not completely understood, the pathophysiology of the disease involves chronic dysregulation of inflammatory and vascular signalling. In the quest for novel therapeutic targets, we investigated the involvement of galectin-1 (Gal-1), an endogenous glycan-binding protein endowed with both immunosuppressive and pro-angiogenic activities, in the pathophysiology of endometriotic lesions. Here we show that Gal-1 is selectively expressed in stromal and endothelial cells of human endometriotic lesions. Using an experimental endometriosis model induced in wild-type and Gal-1-deficient (Lgals1(-/-) ) mice, we showed that this lectin orchestrates the formation of vascular networks in endometriotic lesions in vivo, facilitating their ectopic growth independently of vascular endothelial growth factor (VEGF) and the keratinocyte-derived CXC-motif (CXC-KC) chemokine. Targeting Gal-1 using a specific neutralizing mAb reduced the size and vascularized area of endometriotic lesions within the peritoneal compartment. These results underline the essential role of Gal-1 during endometriosis and validate this lectin as a possible target for the treatment of disease.Fil: Baston, Juan Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Barañao, Rosa Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Ricci, Analía Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Bilotas, Mariela Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Olivares, Carla Noemi. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Singla, José J.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Gonzalez, Alejandro M.. Ministerio de Defensa. Armada Argentina. Hospital Naval Buenos Aires-cirujano Mayor Dr. Pedro Mallo; ArgentinaFil: Stupirski, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Croci Russo, Diego Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Meresman, Gabriela Fabiana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentin