{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:53:23Z","timestamp":1790016803668,"version":"4.0.1"},"reference-count":49,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,9]],"date-time":"2024-03-09T00:00:00Z","timestamp":1709942400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PRIN 2022 PNRR, Settore ERC: LS4","award":["MUR: P2022HB33K-CUP: E53D23019850001"],"award-info":[{"award-number":["MUR: P2022HB33K-CUP: E53D23019850001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Systemic Sclerosis (SSc) is a heterogeneous autoimmune disease characterized by widespread vasculopathy, the presence of autoantibodies and the progressive fibrosis of skin and visceral organs. There are still many questions about its pathogenesis, particularly related to the complex regulation of the fibrotic process, and to the factors that trigger its onset. Our recent studies supported a key role of N-formyl peptide receptors (FPRs) and their crosstalk with uPAR in the fibrotic phase of the disease. Here, we found that dermal fibroblasts acquire a proliferative phenotype after the activation of FPRs and their interaction with uPAR, leading to both Rac1 and ERK activation, c-Myc phosphorylation and Cyclin D1 upregulation which drive cell cycle progression. The comparison between normal and SSc fibroblasts reveals that SSc fibroblasts exhibit a higher proliferative rate than healthy control, suggesting that an altered fibroblast proliferation could contribute to the initiation and progression of the fibrotic process. Finally, a synthetic compound targeting the FPRs\/uPAR interaction significantly inhibits SSc fibroblast proliferation, paving the way for the development of new targeted therapies in fibrotic diseases.<\/jats:p>","DOI":"10.3390\/ijms25063156","type":"journal-article","created":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T06:05:30Z","timestamp":1710137130000},"page":"3156","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Crosstalk between N-Formyl Peptide Receptors and uPAR in Systemic Sclerosis: Molecular Mechanisms, Pathogenetic Role and Therapeutic Opportunities"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1925-9912","authenticated-orcid":false,"given":"Filomena","family":"Napolitano","sequence":"first","affiliation":[{"name":"Department of Translational Medical Sciences, University of Naples Federico II, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5430-032X","authenticated-orcid":false,"given":"Francesca Wanda","family":"Rossi","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Naples Federico II, 80138 Naples, Italy"},{"name":"Center for Basic and Clinical Immunology Research (CISI), WAO Center of Excellence, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0347-2540","authenticated-orcid":false,"given":"Amato","family":"de Paulis","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Naples Federico II, 80138 Naples, Italy"},{"name":"Center for Basic and Clinical Immunology Research (CISI), WAO Center of Excellence, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2181-8026","authenticated-orcid":false,"given":"Antonio","family":"Lavecchia","sequence":"additional","affiliation":[{"name":"\u201cDrug Discovery\u201d Laboratory, Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8697-986X","authenticated-orcid":false,"given":"Nunzia","family":"Montuori","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Naples Federico II, 80138 Naples, Italy"},{"name":"Center for Basic and Clinical Immunology Research (CISI), WAO Center of Excellence, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kowalska-K\u0119pczy\u0144ska, A. 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