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Proteolytic signatures define unique thrombin-derived peptides present in human wound fluid in vivo

Saravanan, Rathi; Adav, Sunil S.; Choong, Yeu Khai; Van Der Plas, Mariena J.A. LU ; Petrlova, Jitka LU ; Kjellström, Sven LU ; Sze, Siu Kwan and Schmidtchen, Artur LU (2017) In Scientific Reports 7(1).
Abstract

The disease burden of failing skin repair and non-healing ulcers is extensive. There is an unmet need for new diagnostic approaches to better predict healing activity and wound infection. Uncontrolled and excessive protease activity, of endogenous or bacterial origin, has been described as a major contributor to wound healing impairments. Proteolytic peptide patterns could therefore correlate and "report" healing activity and infection. This work describes a proof of principle delineating a strategy by which peptides from a selected protein, human thrombin, are detected and attributed to proteolytic actions. With a particular focus on thrombin-derived C-terminal peptides (TCP), we show that distinct peptide patterns are generated in... (More)

The disease burden of failing skin repair and non-healing ulcers is extensive. There is an unmet need for new diagnostic approaches to better predict healing activity and wound infection. Uncontrolled and excessive protease activity, of endogenous or bacterial origin, has been described as a major contributor to wound healing impairments. Proteolytic peptide patterns could therefore correlate and "report" healing activity and infection. This work describes a proof of principle delineating a strategy by which peptides from a selected protein, human thrombin, are detected and attributed to proteolytic actions. With a particular focus on thrombin-derived C-terminal peptides (TCP), we show that distinct peptide patterns are generated in vitro by the human S1 peptidases human neutrophil elastase and cathepsin G, and the bacterial M4 peptidases Pseudomonas aeruginosa elastase and Staphylococcus aureus aureolysin, respectively. Corresponding peptide sequences were identified in wound fluids from acute and non-healing ulcers, and notably, one peptide, FYT21 (FYTHVFRLKKWIQKVIDQFGE), was only present in wound fluid from non-healing ulcers colonized by P. aeruginosa and S. aureus. Our result is a proof of principle pointing at the possibility of defining peptide biomarkers reporting distinct proteolytic activities, of potential implication for improved diagnosis of wound healing and infection.

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author
organization
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type
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publication status
published
subject
in
Scientific Reports
volume
7
issue
1
publisher
Nature Publishing Group
external identifiers
  • scopus:85031681369
  • wos:000412956900026
ISSN
2045-2322
DOI
10.1038/s41598-017-13197-3
language
English
LU publication?
yes
id
b43189d1-7959-4f2d-93fa-9ae443282b71
date added to LUP
2017-10-30 12:37:24
date last changed
2018-01-16 13:24:47
@article{b43189d1-7959-4f2d-93fa-9ae443282b71,
  abstract     = {<p>The disease burden of failing skin repair and non-healing ulcers is extensive. There is an unmet need for new diagnostic approaches to better predict healing activity and wound infection. Uncontrolled and excessive protease activity, of endogenous or bacterial origin, has been described as a major contributor to wound healing impairments. Proteolytic peptide patterns could therefore correlate and "report" healing activity and infection. This work describes a proof of principle delineating a strategy by which peptides from a selected protein, human thrombin, are detected and attributed to proteolytic actions. With a particular focus on thrombin-derived C-terminal peptides (TCP), we show that distinct peptide patterns are generated in vitro by the human S1 peptidases human neutrophil elastase and cathepsin G, and the bacterial M4 peptidases Pseudomonas aeruginosa elastase and Staphylococcus aureus aureolysin, respectively. Corresponding peptide sequences were identified in wound fluids from acute and non-healing ulcers, and notably, one peptide, FYT21 (FYTHVFRLKKWIQKVIDQFGE), was only present in wound fluid from non-healing ulcers colonized by P. aeruginosa and S. aureus. Our result is a proof of principle pointing at the possibility of defining peptide biomarkers reporting distinct proteolytic activities, of potential implication for improved diagnosis of wound healing and infection.</p>},
  articleno    = {13136},
  author       = {Saravanan, Rathi and Adav, Sunil S. and Choong, Yeu Khai and Van Der Plas, Mariena J.A. and Petrlova, Jitka and Kjellström, Sven and Sze, Siu Kwan and Schmidtchen, Artur},
  issn         = {2045-2322},
  language     = {eng},
  month        = {12},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Proteolytic signatures define unique thrombin-derived peptides present in human wound fluid in vivo},
  url          = {http://dx.doi.org/10.1038/s41598-017-13197-3},
  volume       = {7},
  year         = {2017},
}