Galectin-7 is important for normal uterine repair following menstruation

Abstract

Menstruation involves the shedding of the functional layer of the endometrium in the absence of pregnancy. At sites where tissue shedding is complete, re-epithelialization of the tissue is essential for repair and termination of bleeding. The complement of growth factors that mediate post-menstrual endometrial repair are yet to be completely elucidated. Galectins regulate many cell functions important for post-menstrual repair, such as cell adhesion and migration. Galectin-7 has a well characterized role in re-epithelialization and wound healing. We hypothesized that galectin-7 would be important in re-epithelialization during post-menstrual repair. We aimed to identify endometrial expression of galectin-7 in women undergoing normal endometrial repair and in women with amenorrhoea who do not experience endometrial breakdown and repair, and to determine whether galectin-7 enhances endometrial re-epithelialization in vitro. Galectin-7 immunolocalized to the endometrial luminal and glandular epithelium during the late secretory and menstrual phases, and to decidualized stroma in regions exhibiting tissue breakdown. Immunostaining intensity was significantly reduced in the endometrium of women with amenorrhoea compared with normally cycling woman. ELISA identified galectin-7 in menstrual fluid at significantly elevated levels compared with matched peripheral plasma. Exogenous galectin-7 (2.5 µg/ml) significantly enhanced endometrial epithelial wound repair in vitro; this was abrogated by inhibition of integrin binding. Galectin-7 elevated epithelial expression of extracellular matrix-related molecules likely involved in repair including β-catenin, contactin and TGF-β1. In conclusion, galectin-7 is produced by the premenstrual and menstrual endometrium, where it accumulates in menstrual fluid and likely acts as a paracrine factor to facilitate post-menstrual endometrial re-epithelialization.

Transmembrane Mucin Expression and Function in Embryo Implantation and Placentation

“…In addition, elevated galectin-7 expression is associated with uterine repair after menstruation (Evans et al 2014 ), miscarriage (Menkhorst et al 2014b ), and preeclampsia (Menkhorst et al 2014a ). Many of these observations relate to the proposed role for galectin-7 in reepithelialization associated with wound repair (Panjwani 2014 ).…”

High expression of galectin-7 associates with poor overall survival in patients with non-metastatic clear-cell renal cell carcinoma

“…However, in cancerous renal tissue, galectin-7 may manifest completely different functions. Take the uterus for examples, galectin-7 up-regulate MMP-9 expression, thereby promotes tumor progression and metastasis in cervical squamous carcinoma [25], while in normal uterus, it promotes uterine repair following menstruation [26]. Our study revealed the correlation of galectin-7 expression and overall survival in non-metastasis ccRCC, which shed a light on the potentially different functions of galectin-7 in ccRCC from normal kidney tissues.…”

Galectin‑7 is elevated in endometrioid (type I) endometrial cancer and promotes cell migration

“…It was hypothesized that the recombinant galectin-7 utilized in the present study would have extra-and intra-cellular actions. We have previously demonstrated that endometrial epithelial cell lines display functional responses to exogenous galectin-7 (14,15). Whether exogenous galectin-7 is endocytozed into EC cells is yet to be determined: An increase in intracellular galectin-7 mRNA in Ishikawa cells 24 h after galectin-7 treatment was not identified (data not shown); however, only one time-point was used and intracellular protein was not measured.…”

“…To mimic the rising levels of galectin-7 determined in EC, EC cell lines were treated with recombinant galectin-7 for the in vitro functional assays. The concentration used (1 µg/ml) was determined from the manufacturer's protocols and dose-response trials in previous studies (14,15), but it is notable that extracellular galectin-7 remains to be identified in EC. Galectin-7 could not be detected in the endometrial epithelial EC cell line conditioned media (data not shown).…”

“…Additionally, it accelerates the re-epithelialization of corneal wounds more efficiently than the majority of known growth factors (12,13). In the uterus, galectin-7 promotes wound repair following menstruation (14) and elevated endometrial epithelial galectin-7 is associated with miscarriage, possibly due to its role as an anti-adhesion molecule during implantation (15).…”