Aspartic proteases are abundant and active in acidified wound fluid
Barbosa da Silva, E.; Crane, M.; Liu, L.; Gelsinger, D. J.; Jordon, A.; McKinney, R. L.; Eberson, C. P.; Jamieson, A.; O'Donoghue, A. J.
Show abstract
Wound healing necessitates a balance between synthesis and breakdown of extracellular matrix components, which is tightly regulated by proteases and their inhibitors. Studies have shown that treatment of poorly healing wounds with acid results in improved healing. In this study, we systematically evaluated changes in proteolytic activity of murine wound fluid upon acidification. A library of 228 synthetic peptides served as reporters of protease activity at pH 7.4, pH 5.0 and pH 3.5. The peptide digestion patterns differed at each pH, revealing that proteases active at pH 7.4 are inactivated at pH 3.5. Notably, aspartic acid proteases emerged as the dominant active enzymes at pH 3.5 and their activity was inhibited by pepstatin. Using a fluorogenic substrate, we quantified aspartic protease activity across varying pH levels and demonstrated optimal activity between pH 3.0 and 3.8. This activity was detectable as early as one day post-injury and persisted over the following ten days. Importantly, human wound fluid exhibited the same activity profile, validating the mouse model as a relevant system for studying acid-mediated wound healing processes.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Nebulized and intravenous enzyme replacement therapy in mice with mucopolysaccharidosis type II 93%
- Generation and characterization of two immortalized dermal fibroblast cell lines from the spiny mouse (Acomys) 93%
- Heterogeneity in Proline Hydroxylation of Fibrillar Collagens Observed by Mass Spectrometry 93%
Similar papers in this journal
- Re-evaluation of lysyl hydroxylation in the collagen triple helix: lysyl hydroxylase 1 and prolyl 3-hydroxylase 3 have site-differential and collagen type-dependent roles in lysine hydroxylation. 92%
- High affinity binding of SARS-CoV-2 spike protein enhances ACE2 carboxypeptidase activity 91%
- Versican binds collagen via its G3 domain and regulates the organization and mechanics of collagenous matrices 91%
Similar papers in this journal
- Local Shifts in Inflammatory and Resolving Lipid Mediators in Response to Tendon Overuse 92%
- Spatial mapping of dextran sodium sulphate-induced intestinal inflammation and its systemic effects 92%
- The Connexin 43 Carboxyl Terminal Mimetic Peptide alphaCT1 Prompts Differentiation of a Collagen Scar Matrix Resembling Unwounded Skin 92%
"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.