Prolidase Function in Collagen Metabolism
Summary
Prolidase, also known as peptidase D, is the sole cytosolic metalloproteinase capable of cleaving dipeptides that terminate in proline or hydroxyproline. By liberating free proline from collagen breakdown products, prolidase orchestrates a critical recycling step in collagen turnover. This regenerated proline serves as a substrate for new collagen synthesis, maintaining extracellular matrix integrity and supporting tissue remodelling. Beyond its catalytic role, prolidase has been shown to modulate cell signalling pathways, acting as a ligand for surface receptors and influencing processes such as cell proliferation, migration and angiogenesis. Dysregulation of prolidase activity underlies impaired wound healing, chronic ulcers and fibrotic disorders, while genetic loss of function causes prolidase deficiency, a multisystem disorder marked by defective collagen recycling, immune dysfunction and skin ulcerations. Recent advances have illuminated both the enzymatic mechanics and non-enzymatic functions of prolidase, expanding its significance in physiology and disease.
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Prolidase Function in Collagen Metabolism publication trend
The graph below shows the total number of articles in prolidase function in collagen metabolism across all publications each year (not limited to Nature Index journals).
Technical terms
Prolidase (PEPD): A cytosolic metalloproteinase that cleaves dipeptides with a C-terminal proline or hydroxyproline, crucial for collagen recycling.
Extracellular matrix (ECM): A complex network of proteins and carbohydrates that provides structural and biochemical support to surrounding cells.
Epidermal growth factor receptor (EGFR): A cell-surface receptor kinase that, upon ligand binding, activates signalling cascades regulating proliferation and migration.
Transforming growth factor-β1 (TGF-β1): A cytokine that modulates extracellular matrix production and fibrogenesis through transcriptional regulation.
Specificity protein 1 (Sp1): A transcription factor that recognises GC-rich promoter sequences, essential for basal gene expression including PEPD.
Krüppel-like factor 6 (KLF6): A zinc-finger transcription factor that cooperates with Sp1 to regulate genes involved in extracellular matrix synthesis.
Recombinant human prolidase (rhPEPD): Laboratory-produced prolidase used in experimental models to evaluate therapeutic potential in wound healing.
References
- Recombinant Human Prolidase (rhPEPD) Induces Wound Healing in Experimental Model of Inflammation through Activation of EGFR Signalling in Fibroblasts. Molecules (2023).
- KLF6 activates Sp1-mediated prolidase transcription during TGF-β1 signaling. Journal of Biological Chemistry (2023).
- Prolidase Directly Binds and Activates Epidermal Growth Factor Receptor and Stimulates Downstream Signaling*. Journal of Biological Chemistry (2012).
- PROLIDASE: A Review from Discovery to its Role in Health and Disease. Frontiers in Molecular Biosciences (2021).
- Clinical Genetics of Prolidase Deficiency: An Updated Review. Biology (2020).
- Current Understanding of the Emerging Role of Prolidase in Cellular Metabolism. International Journal of Molecular Sciences (2020).
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