Lysyl oxidase-dependent bone marrow stiffening promotes neutrophil activation in diabetes
Agarwal, M.; Chandrakumar, S.; Trada, V.; Srivastava, S.; Ghosh, K.
Show 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 {beta}-aminopropionitrile (BAPN) in diabetic mice concomitantly blocked BM matrix stiffening and neutrophil activation (superoxide generation and gp91phox upregulation), which predictably inhibited neutrophil cytotoxicity towards co-cultured retinal endothelial cells. Further, culturing neutrophils within BM-mimicking hydrogels of tunable stiffness indicate that matrix-localized and soluble LOX act synergistically to mechanochemically activate neutrophils in the BM. Thus, LOX-dependent changes in the BM physical environment offer a new mechanistic basis and therapeutic target for diabetic complications marked by neutrophil activation.
Matching journals
The top 11 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Fractalkine-induced microglial vasoregulation occurs within the retina and is altered early in diabetic retinopathy 94%
- Corticosteroids prevent pathological angiogenesis yet compromise reparative vascular remodeling in the retina 93%
- Monocytes use protrusive forces to generate migration paths in viscoelastic collagen-based extracellular matrices 92%
Similar papers in this journal
- An endothelial SOX18-mevalonate pathway axis enables repurposing of statins for infantile hemangioma 91%
- Angiopoietin-like protein 2 mediates vasculopathy driven fibrogenesis in a mouse model of systemic sclerosis 90%
- RAB7 deficiency impairs pulmonary artery endothelial function and promotes pulmonary hypertension 90%
Similar papers in this journal
Similar papers in this journal
- C1q limits cystoid edema by maintaining basal beta-catenin-dependent signaling and blood-retina barrier function 92%
- Myeloid Drp1 Deficiency Limits Revascularization in Ischemic Muscles via Inflammatory Macrophage Polarization and Metabolic Reprograming 92%
- Inhibition of histone readers bromodomain extra-terminal proteins alleviates skin fibrosis in experimental models of scleroderma 91%
Similar papers in this journal
- Reconstituted high-density lipoproteins rescue diabetes-impaired endothelial cell metabolic reprograming and angiogenic responses to hypoxia 94%
- Single-Cell Multimodal Profiling Highlights Persistent Aortic Smooth Muscle Cell Changes in Diabetic Mice Despite Glycemic Control 91%
- A Novel Angiogenesis Role of GLP-1(32-36) to Rescue Diabetic Ischemic Lower Limbs via GLP-1R-Dependent Glycolysis 91%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.