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Multimerin1, not Galectin-8, Promotes Gastric Chief Cell Differentiation by Tempering WNT Signaling

Created on 06 Nov 2025

Authors

Lin, X., Nicolazzi, G. A., Liu, X., Nwokolo, C., Zick, Y., Saenz, J., Brown, J. W.

Abstract

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 cell 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 an unappreciated deletion of Mmrn1 and Snca in the Lgals8-/- line. We show that multimerin-1 tempers WNT stimulation of the gastric corpus at early age as evidenced by Beta-Catenin staining and proliferation throughout the gland. 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 overlapping functions of galectin-8 and multimerin-1, future studies using pure knockouts are necessary to refine these phenotypes.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 06 Nov 2025.

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