{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T21:39:41Z","timestamp":1789681181872,"version":"4.0.1"},"reference-count":68,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,14]],"date-time":"2023-01-14T00:00:00Z","timestamp":1673654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Centre of Science, Poland","award":["2017\/25\/B\/NZ7\/02650"],"award-info":[{"award-number":["2017\/25\/B\/NZ7\/02650"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The potential of recombinant human prolidase (rhPEPD) to induce wound healing in an experimental model of IL-1\u03b2-induced inflammation in human fibroblasts was studied. It was found that rhPEPD significantly increased cell proliferation and viability, as well as the expression of the epidermal growth factor receptor (EGFR) and downstream signaling proteins, such as phosphorylated PI3K, AKT, and mTOR, in the studied model. Moreover, rhPEPD upregulated the expression of the \u03b21 integrin receptor and its downstream signaling proteins, such as p-FAK, Grb2 and p-ERK 1\/2. The inhibition of EGFR signaling by gefitinib abolished rhPEPD-dependent functions in an experimental model of inflammation. Subsequent studies showed that rhPEPD augmented collagen biosynthesis in IL-1\u03b2-treated fibroblasts as well as in a wound healing model (wound closure\/scratch test). Although IL-1\u03b2 treatment of fibroblasts increased cell migration, rhPEPD significantly enhanced this process. This effect was accompanied by an increase in the activity of MMP-2 and MMP-9, suggesting extracellular matrix (ECM) remodeling during the inflammatory process. The data suggest that rhPEPD may play an important role in EGFR-dependent cell growth in an experimental model of inflammation in human fibroblasts, and this knowledge may be useful for further approaches to the treatment of abnormalities of wound healing and other skin diseases.<\/jats:p>","DOI":"10.3390\/molecules28020851","type":"journal-article","created":{"date-parts":[[2023,1,16]],"date-time":"2023-01-16T04:57:19Z","timestamp":1673845039000},"page":"851","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Recombinant Human Prolidase (rhPEPD) Induces Wound Healing in Experimental Model of Inflammation through Activation of EGFR Signalling in Fibroblasts"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5263-4115","authenticated-orcid":false,"given":"Weronika","family":"Baszanowska","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Niziol","sequence":"additional","affiliation":[{"name":"Department of Analysis and Bioanalysis of Medicines, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7934-6973","authenticated-orcid":false,"given":"Ilona","family":"Oscilowska","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justyna","family":"Czyrko-Horczak","sequence":"additional","affiliation":[{"name":"Department of Structural Chemistry, Faculty of Chemistry, University of Bialystok, Ciolkowskiego 1K, 15-245 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5150-6093","authenticated-orcid":false,"given":"Wojciech","family":"Miltyk","sequence":"additional","affiliation":[{"name":"Department of Analysis and Bioanalysis of Medicines, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8476-2023","authenticated-orcid":false,"given":"Jerzy","family":"Palka","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, Medical University of Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,14]]},"reference":[{"key":"ref_1","first-page":"31","article-title":"Proline-dependent structural and biological properties of peptides and proteins","volume":"28","author":"Yaron","year":"1993","journal-title":"Biochem. 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