The luteotrophic function of galectin-1 by binding to the glycans on vascular endothelial growth factor receptor-2 in bovine luteal cells

Abstract

The corpus luteum (CL) is a temporary endocrine gland producing a large amount of progesterone, which is essential for the establishment and maintenance of pregnancy. Galectin-1 is a β-galactose-binding protein that can modify functions of membrane glycoproteins and is expressed in the CL of mice and women. However, the physiological role of galectin-1 in the CL is unclear. In the present study, we investigated the expression and localization of galectin-1 in the bovine CL and the effect of galectin-1 on cultured luteal steroidogenic cells (LSCs) with special reference to its binding to the glycans on vascular endothelial growth factor receptor-2 (VEGFR-2). Galectin-1 protein was highly expressed at the mid and late luteal stages in the membrane fraction of bovine CL tissue and was localized to the surface of LSCs in a carbohydrate-dependent manner. Galectin-1 increased the viability in cultured LSCs. However, the viability of LSCs was decreased by addition of β-lactose, a competitive carbohydrate inhibitor of galectin-1 binding activity. VEGFR-2 protein, like galectin-1, is also highly expressed in the mid CL, and it was modified by multi-antennary glycans, which can be recognized by galectin-1. An overlay assay using biotinylated galectin-1 revealed that galectin-1 directly binds to asparagine-linked glycans (N-glycans) on VEGFR-2. Enhancement of LSC viability by galectin-1 was suppressed by a selective inhibitor of VEGFR-2. The overall findings suggest that galectin-1 plays a role as a survival factor in the bovine CL, possibly by binding to N-glycans on VEGFR-2.

O‐glycan structures in apo(a) subunit of human lipoprotein(a) suppresses the pro‐angiogenic activity of galectin‐1 on human umbilical vein endothelial cells

“…The O‐glycan‐mediated binding of galectin‐1 to NRP‐1 further activates another angiogenic protein, vascular endothelial growth factor receptor 2 (VEGFR2). In fact, galectin‐1 can directly bind to the LacNAc residues in VEGFR2 21 . As a result, the downstream proteins of mitogen‐activated protein kinases (MAPK) signaling pathway get activated eventually leading to the activation of angiogenic processes such as proliferation, migration, and tube formation in endothelial cells 14,21–26 .…”

“…21 As a result, the downstream proteins of mitogen-activated protein kinases (MAPK) signaling pathway get activated eventually leading to the activation of angiogenic processes such as proliferation, migration, and tube formation in endothelial cells. 14,[21][22][23][24][25][26] An earlier report demonstrated that the inhibition of galectin-1-stimulated angiogenesis with anginex, a designed anti-angiogenic peptide, leads to impaired angiogenesis and poor placentation and provokes pre-eclampsialike symptoms with intrauterine fetal growth restriction in mice. 25 Pre-eclampsia is a vascular disease of the placenta that arises during pregnancy in association with hypertension and proteinuria.…”