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bioRxiv · 10.1101/2025.11.04.685347

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

Lin, X.·Nicolazzi, G. A.·Liu, X.·Nwokolo, C.·Zick, Y.·Saenz, J.·Brown, J. W.
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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 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 and 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 an early age, as evidenced by nuclear 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 galectin-8 and multimerin-1 have overlapping functions albeit, divergent with respect to bone, future studies using pure knockouts are necessary to refine these phenotypes.

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Lin, X., Nicolazzi, G. A., Liu, X., Nwokolo, C., Zick, Y., Saenz, J., Brown, J. W.. 2025-11-05. Multimerin1, not Galectin-8, Promotes Gastric Chief Cell Differentiation by Tempering WNT Signaling. https://doi.org/10.1101/2025.11.04.685347

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