Decorin

Decorin is a small leucine-rich proteoglycan (SLRP) that functions both as a structural component of the extracellular matrix (ECM) and as a signaling molecule. PMID 29435195 It consists of a protein core composed of leucine-rich repeats with a dermatan sulfate glycosaminoglycan side chain attached at its N-terminus. PMID 22877511PMID 32354384

Decorin's primary structural role involves regulating collagen fibrillogenesis by binding to collagen fibrils, ensuring they are uniformly sized and regularly spaced—particularly critical for corneal transparency. PMID 21342131 Beyond this matrix-organizing function, decorin acts as a multifunctional signaling molecule through several mechanisms:

Growth factor modulation: Decorin binds and sequesters transforming growth factor-beta (TGF-β), a key regulator of fibrosis, thereby exerting potent anti-fibrotic effects PMID 29435195PMID 40279258PMID 21342131

Receptor tyrosine kinase (RTK) inhibition: It functions as a pan-RTK inhibitor, binding to and downregulating multiple receptors including EGFR, HER2, Met, VEGFR2, and IGF-R, leading to growth suppression and anti-tumorigenic effects PMID 35171698PMID 22735579PMID 18798267

Anti-angiogenic activity: Through VEGFR2 interaction, decorin inhibits angiogenesis and induces endothelial cell autophagy PMID 26522384

Decorin is considered a myokine (a type of exerkine). Decorin is released from contracting skeletal muscle and its circulating levels increase in response to acute resistance exercise in humans. PMID 24996176 Furthermore, decorin expression in skeletal muscle increases after chronic training in both humans and mice. PMID 24996176

• Contraction-induced release: Decorin is released from contracting human myotubes in vitro PMID 24996176
• Exercise-responsive expression: Both acute and chronic exercise increase decorin levels systemically and in muscle tissue PMID 24996176
• Functional role in muscle: Decorin promotes muscle hypertrophy by binding myostatin (a muscle growth inhibitor) and upregulating pro-myogenic factors like Myod1 and follistatin while reducing atrophic markers PMID 24996176

This myokine function positions decorin as a mediator of exercise's beneficial effects on muscle remodeling and potentially systemic health outcomes.

Decorin functions as a pan-receptor tyrosine kinase inhibitor and has shown oncosuppressive effects by binding to multiple receptor tyrosine kinases (EGFR, HER2, Met, VEGFR2, IGFR) and inhibiting downstream signaling pathways that promote tumor growth, angiogenesis, and metastasis. PMID 26522384PMID 35171698PMID 39954173 Studies indicate decorin suppresses tumorigenic growth and prevents metastatic lesions in various in vitro and in vivo tumor models. PMID 26522384PMID 26697491PMID 18798267

As an antifibrotic agent, decorin primarily inhibits transforming growth factor-β (TGF-β), a major driver of fibrosis in multiple organs including heart, liver, skin, and muscle. PMID 40279258 Therapeutic applications using recombinant protein, gene-delivery systems, and decorin-loaded hydrogels have demonstrated potential for both localized and systemic fibrosis treatment. PMID 40279258 Decorin has shown efficacy in preventing epidural fibrosis and adhesions after laminectomy by suppressing TGF-β1-induced fibroblast proliferation and extracellular matrix production via the Smad2/3 signaling pathway. PMID 34975478

In cardiovascular disease, decorin improves cardiac function following myocardial infarction through anti-inflammatory and anti-apoptotic effects, with studies showing improved cardiac hemodynamics, reduced oxidative stress, and decreased expression of inflammatory markers (TNF-α, IL-1β, TGF-β1). PMID 36917819

Decorin also plays a role in autoimmune and inflammatory diseases, including inflammatory bowel disease, rheumatoid arthritis, systemic sclerosis, and multiple sclerosis, through immune regulation mechanisms. PMID 36033387