Galectins are a family of proteins that bind galactose-containing glycans. One member, galectin-8, preferentially binds galactose that contains a terminal sulfate. Aberrant expression and secretion of sulfated glycosylation epitopes, such as 3'-Sulfo-LeA/C, is a feature of high-risk human foregut metaplasias. In addition, recent work has demonstrated that 3'-Sulfo-LeC is a marker of mature murine zymogenic chief cells of the stomach and that 3'-Sulfo-LeC epitope is secreted via cathartocytosis during the cellular transition to a metaplastic state. Based on those findings, we used Lgals8-/- mice, to determine whether galectin-8 might play a role in chief cell homeostasis. We observed delayed gastric differentiation in the Lgals8-/- mice but discovered that this phenotype was due to unappreciated deletions of Mmrn1 and Snca in the Lgals8-/- line and not Lgals8. Since, we could not find evidence of alpha-synuclein at either the RNA or protein level in the stomach, we attributed this phenotype to the absence MMRN1. Our data suggest that multimerin-1 tempers WNT stimulation of the gastric corpus at an early age, as evidenced by nuclear beta-catenin staining and proliferation throughout the gland in Mmrn1-/-/Snca-/- mice. Because multimerin-1 is synthesized and secreted from endothelial cells and not from the epithelial compartment, these data uncover a role for mesodermal cells in epithelial developmental and maturation of the mouse stomach. As prior studies have suggested galectin-8 and multimerin-1 exert opposite effects on bone physiology as well as parallel functions in coagulation, future studies using pure knockouts are necessary to refine these phenotypes.
Lin et al. (Thu,) studied this question.