PI3K/AKT pathway is altered in the endometriosis patient's endometrium and presents differences according to severity stage.

Based on the inflammatory nature and hormone-dependency of endometriosis, PI3K/AKT signaling appears to influence its progression. Could the endometriosis stages be linked to differential changes in PI3K/AKT pathway regulation? The objective is to evaluate the expression of PI3K, PTEN, AKT and p-AKT in endometrial human biopsies, according to the presence or absence of the disease, and to assess the underlying differences regarding the endometriosis stages. Biopsy specimens of the ectopic and eutopic endometrium were obtained from twenty women with untreated peritoneal endometriosis as well as endometrium biopsies from nine controls. Our study revealed an increased expression of PI3K in eutopic and ectopic endometrium from patients with endometriosis, and a reduced expression of PTEN and increased levels of AKT phosphorylation, compared to control endometrium. Both eutopic and ectopic endometrium from patients with minimal-mild endometriosis expressed a significant reduced PTEN level compared to the respective endometrium from patients with moderate-severe endometriosis. The ratio p-AKT/total AKT showed higher levels of AKT phosphorylation in endometriotic tissue from patients with minimal-mild endometriosis. This study has firmly confirmed the alteration in PI3K/AKT pathway regulation and demonstrated clear differences between the stages of endometriosis, emphasizing the importance of this pathway in the first stage of the disease.

Daily expression of sodium-dependent glucose cotransporter-1 protein in jejunum during rat ontogeny.

It is widely known that intestinal capacities such as the enzymatic hydrolysis of carbohydrates, lipids and proteins, and the subsequent absorption of the hydrolyzed products, are evolutionary matched to dietary loads and feeding behaviors. In this study, we demonstrate that the protein expression of apically located sodium-dependent glucose cotransporter-1 (SGLT-1) throughout rat ontogeny is daily adjusted to afford glucose uptake when the load of this metabolically essential monosaccharide in the intestinal lumen is maximum. The jejunal expression of SGLT-1 protein in 14 one-day-old suckling pups was found to increase at dark and early light phase (P < 0.05), when they have a better access to mother milk. In weaning 21-d-old and juvenile 28-d-old rats, the cotransporter expression was high throughout the entire day (P < 0.05). Finally, adult 90-d-old rats showed a well-developed circadian rhythm for SGLT-1 protein (P < 0.05), whose expression increased at late light and dark phase when the highest intestinal glucose load was achieved. To our knowledge, these results are the first reporting the daily profile of SGLT-1 expression during rat early developmental stage and may contribute to understand the biological significance of a well-established molecular capacity to deal with the crucial increase of glucose load in the diet during the weaning process.

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.