Heparan sulfate-dependent RAGE oligomerization is indispensable for pathophysiological functions of RAGE.

ABSTRACT: RAGE, a druggable inflammatory receptor, is known to function as an oligomer but the exact oligomerization mechanism remains poorly understood. Previously we have shown that heparan sulfate (HS) plays an active role in RAGE oligomerization. To understand the physiological significance of HS-induced RAGE oligomerization in vivo, we generated RAGE knock-in mice (Ager^AHA/AHA) by introducing point mutations to specifically disrupt HS-RAGE interaction. The RAGE mutant demonstrated normal ligand-binding but impaired capacity of HS-binding and oligomerization. Remarkably, Ager^AHA/AHA mice phenocopied Ager^-/- mice in two different pathophysiological processes, namely bone remodeling and neutrophil-mediated liver injury, which demonstrates that

SUBMITTER: Li M 

PROVIDER: S-EPMC8863369 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature