Assembly and remodeling of collagen and elastic fibers in pathophysiology: Proteases have the final cut - PubMed
4 hours ago
- #proteases
- #extracellular matrix
- #connective tissue
- Proteases are key regulators in the assembly and turnover of collagen and elastic fibers in the extracellular matrix (ECM).
- Metalloproteinases (BMP1/tolloid-like, meprin, ADAMTS) and lysyl oxidases orchestrate procollagen maturation and cross-linking of collagen and elastin fibers.
- Matrix metalloproteinases (MMPs) and cysteine cathepsins modulate collagen structure and degradation, generating bioactive fragments used as clinical biomarkers.
- ADAMTS and ADAMTS-like proteases regulate fibrillin microfibril organization and elastogenesis topography.
- Elastolytic proteases (cathepsins K, S, V; MMP2, 7, 9, 12) mediate physiological remodeling but can fuel pathological states when dysregulated.
- Dysregulation of proteolytic pathways underlies connective tissue diseases like osteogenesis imperfecta, Ehlers-Danlos syndrome, fibrosis, emphysema, and vascular aging.
- Novel therapeutic strategies include substrate- and exosite-selective inhibitors to restore ECM homeostasis and minimize off-target effects.