Lysyl oxidase-dependent bone marrow stiffening promotes neutrophil activation in diabetes.

ABSTRACT: Persistent neutrophil activation contributes to the development of diabetic vascular complications in many organs including the retina. Past studies have implicated abnormal molecular or biochemical cues in neutrophil activation. Here we show that neutrophils can also be mechanically activated through an increase in bone marrow (BM) stiffness that results from diabetes-induced overexpression of matrix collagens and their crosslinker lysyl oxidase (LOX). Administration of LOX inhibitor β-aminopropionitrile (BAPN) in diabetic mice concomitantly blocked BM matrix stiffening and neutrophil activation (superoxide generation and gp91^phox upregulation), which predictably inhibited neutrophil cytotoxicity towards co-cultured retinal endothelial cells. Further, culturing neutrophils with

SUBMITTER: Agarwal M 

PROVIDER: S-EPMC12424689 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature