ILB® resolves inflammatory scarring and promotes functional tissue repair.
Adrian C WilliamsHannah F BotfieldGhazala BegumOmar QureshiVasanthy VigneswaraImran MasoodNicholas M BarnesLars BruceAnn LoganPublished in: NPJ Regenerative medicine (2021)
Fibrotic disease is a major cause of mortality worldwide, with fibrosis arising from prolonged inflammation and aberrant extracellular matrix dynamics. Compromised cellular and tissue repair processes following injury, infection, metabolic dysfunction, autoimmune conditions and vascular diseases leave tissues susceptible to unresolved inflammation, fibrogenesis, loss of function and scarring. There has been limited clinical success with therapies for inflammatory and fibrotic diseases such that there remains a large unmet therapeutic need to restore normal tissue homoeostasis without detrimental side effects. We investigated the effects of a newly formulated low molecular weight dextran sulfate (LMW-DS), termed ILB®, to resolve inflammation and activate matrix remodelling in rodent and human disease models. We demonstrated modulation of the expression of multiple pro-inflammatory cytokines and chemokines in vitro together with scar resolution and improved matrix remodelling in vivo. Of particular relevance, we demonstrated that ILB® acts, in part, by downregulating transforming growth factor (TGF)β signalling genes and by altering gene expression relating to extracellular matrix dynamics, leading to tissue remodelling, reduced fibrosis and functional tissue regeneration. These observations indicate the potential of ILB® to alleviate fibrotic diseases.
Keyphrases
- extracellular matrix
- oxidative stress
- transforming growth factor
- gene expression
- epithelial mesenchymal transition
- stem cells
- systemic sclerosis
- endothelial cells
- idiopathic pulmonary fibrosis
- multiple sclerosis
- coronary artery disease
- risk assessment
- climate change
- cardiovascular disease
- high resolution
- long non coding rna
- mass spectrometry
- risk factors