{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T10:46:07Z","timestamp":1792233967273,"version":"4.4.0"},"reference-count":104,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T00:00:00Z","timestamp":1672790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gas6 (growth arrest-specific gene 6) is a widely expressed vitamin K-dependent protein that is involved in many biological processes such as homeostatic regulation, inflammation and repair\/fibrotic processes. It is known that it is the main ligand of TAMs, a tyrosine kinase receptor family of three members, namely MerTK, Tyro-3 and Axl, for which it displays the highest affinity. Gas6\/TAM axis activation is known to be involved in modulating inflammatory responses as well as fibrotic evolution in many different pathological conditions. Due to the rapidly evolving COVID-19 pandemic, this review will focus on Gas6\/TAM axis activation in SARS-CoV-2 infection, where de-regulated inflammatory responses and fibrosis represent a relevant feature of severe disease manifestation. Furthermore, this review will highlight the most recent scientific evidence supporting an unsuspected role of Axl as a SARS-CoV-2 infection driver, and the potential therapeutic advantages of the use of existing Axl inhibitors in COVID-19 management. From a physiological point of view, the Gas6\/TAM axis plays a dual role, fostering the tissue repair processes or leading to organ damage and loss of function, depending on the prevalence of its anti-inflammatory or profibrotic properties. This review makes a strong case for further research focusing on the Gas6\/TAM axis as a pharmacological target to manage different disease conditions, such as chronic fibrosis or COVID-19.<\/jats:p>","DOI":"10.3390\/ijms24020951","type":"journal-article","created":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T06:33:44Z","timestamp":1672814024000},"page":"951","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Gas6\/TAM Axis Involvement in Modulating Inflammation and Fibrosis in COVID-19 Patients"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6174-7111","authenticated-orcid":false,"given":"Manuela","family":"Rizzi","sequence":"first","affiliation":[{"name":"Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale (UPO), 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0836-0890","authenticated-orcid":false,"given":"Stelvio","family":"Tonello","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale (UPO), 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3196-940X","authenticated-orcid":false,"given":"Davide","family":"D\u2019Onghia","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale (UPO), 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8322-9158","authenticated-orcid":false,"given":"Pier Paolo","family":"Sainaghi","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, Universit\u00e0 del Piemonte Orientale (UPO), 28100 Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.3389\/fmed.2018.00137","article-title":"GAS6\/TAM pathway signaling in hemostasis and thrombosis","volume":"5","author":"Law","year":"2018","journal-title":"Front. 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