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Moreover, fibroblasts, which are key players in fibrosis, are parasite target cells in a Besnoitia besnoiti chronic infection. This study aimed to decipher the molecular basis that underlies a drift toward fibrosis during the disease progression. Transcriptomic analysis was developed at two times post-infection (p.i.), representative of invasion (12 h p.i.) and intracellular proliferation (32 h p.i.), in primary bovine aorta fibroblasts infected with B. besnoiti tachyzoites. Once the enriched host pathways were identified, we studied the expression of selected differentially expressed genes (DEGs) in the scrotal skin of sterile infected bulls. Functional enrichment analyses of DEGs revealed shared hallmarks of cancer and early fibrosis. Biomarkers of inflammation, angiogenesis, cancer, and MAPK signaling stood out at 12 h p.i. At 32 h p.i., again MAPK and cancer pathways were enriched together with the PI3K\u2013AKT pathway related to cell proliferation. Some DEGs were also regulated in the skin samples of naturally infected bulls (PLAUR, TGF\u03b21, FOSB). We have identified potential biomarkers and host pathways regulated during fibrosis that may hold prognostic significance and could emerge as potential therapeutic targets.<\/jats:p>","DOI":"10.3390\/microorganisms12030586","type":"journal-article","created":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T12:02:39Z","timestamp":1710504159000},"page":"586","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Transcriptomics of Besnoitia besnoiti-Infected Fibroblasts Reveals Hallmarks of Early Fibrosis and Cancer Progression"],"prefix":"10.3390","volume":"12","author":[{"given":"Mar\u00eda","family":"Fern\u00e1ndez-\u00c1lvarez","sequence":"first","affiliation":[{"name":"SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9758-7765","authenticated-orcid":false,"given":"Pilar","family":"Horcajo","sequence":"additional","affiliation":[{"name":"SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Jim\u00e9nez-Mel\u00e9ndez","sequence":"additional","affiliation":[{"name":"SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo Angulo","family":"Lara","sequence":"additional","affiliation":[{"name":"SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9627-7658","authenticated-orcid":false,"given":"Ana","family":"Huertas-L\u00f3pez","sequence":"additional","affiliation":[{"name":"SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, 28040 Madrid, Spain"},{"name":"Animal Health Department, Faculty of Veterinary Sciences, University of Murcia\u2014Regional Campus of International Excellence \u201cCampus Mare Nostrum\u201d, 30100 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Huertas-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Marbyt\u2014Smart Solutions for Biotechnology, 30100 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Ferre","sequence":"additional","affiliation":[{"name":"SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4986-6783","authenticated-orcid":false,"given":"Luis Miguel","family":"Ortega-Mora","sequence":"additional","affiliation":[{"name":"SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6627-7577","authenticated-orcid":false,"given":"Gema","family":"\u00c1lvarez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"SALUVET, Animal Health Department, Faculty of Veterinary Sciences, Complutense University of Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"European Food Safety Authority (2010). 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