# The Receptor for Advanced Glycation End-Products (RAGE) Regulates Cell Adhesion Through Upregulation of ITGA8

## TL;DR

This study shows that RAGE, a receptor involved in inflammation, also regulates cell adhesion by influencing ITGA8 expression.

## Contribution

The study identifies a novel role of RAGE in cell adhesion through its cytoplasmic domain's regulation of ITGA8.

## Key findings

- RAGE exhibits substrate-specific adhesion to extracellular matrix proteins.
- The intracellular domain of RAGE is essential for modulating cell spreading.
- ITGA8 regulation depends on the cytoplasmic domain of RAGE.

## Abstract

The Receptor for Advanced Glycation End-Products (RAGE) is a cell surface receptor of the immunoglobulin-like receptor superfamily. RAGE is a pattern-recognition, multi-ligand receptor that binds glycated proteins, specific non-glycated proteins, and nucleic acids. RAGE ligands are typically part of the group of damage-associated molecular patterns (DAMPs) or alarmins. As such, RAGE is a receptor for molecular products of cellular stress, abnormal metabolism, and inflammation. Activation of RAGE by its ligands leads to pro-inflammatory signaling, often resulting in persistent RAGE activation in various disease states. Consequently, RAGE has been investigated as a potential drug target in the treatment of diabetic complications, vascular disease, Alzheimer’s disease, and multiple types of cancer. An underexplored aspect of RAGE is its role in cell adhesion. Structural comparison of the extracellular domain of RAGE has revealed structural similarity to the activated leukocyte cell adhesion molecule (ALCAM). The present study reveals the role and mechanism of RAGE in regulating cell adhesion. We investigated the role of individual RAGE domains in cell adhesion to extracellular matrix proteins and the changes in protein expression resulting from RAGE upregulation. Key findings include that RAGE displays substrate-specific adhesion to extracellular matrix proteins, that the intracellular domain of RAGE is required for modulating cell spreading, and that regulation of ITGA8 depends on the cytoplasmic domain of RAGE.