RT Journal Article
T1 Transcriptomics of Besnoitia besnoiti-Infected Fibroblasts Reveals Hallmarks of Early Fibrosis and Cancer Progression
A1 Fernández Álvarez, María
A1 Horcajo Iglesias, María Del Pilar
A1 Jiménez Meléndez, Alejandro
A1 Ferré Pérez, Ignacio
A1 Ortega Mora, Luis Miguel
A1 Álvarez García, Gema
A1 Angulo Lara, Pablo
A1 Huertas López, Ana
A1 Huertas López, Francisco
AB Endothelial injury, inflammatory infiltrate and fibrosis are the predominant lesions in the testis of bulls with besnoitiosis that may result in sterility. 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–AKT pathway related to cell proliferation. Some DEGs were also regulated in the skin samples of naturally infected bulls (PLAUR, TGFβ1, FOSB). We have identified potential biomarkers and host pathways regulated during fibrosis that may hold prognostic significance and could emerge as potential therapeutic targets.
PB MDPI
SN 2076-2607
YR 2024
FD 2024-03-15
LK https://hdl.handle.net/20.500.14352/103141
UL https://hdl.handle.net/20.500.14352/103141
LA eng
NO Fernández-Álvarez, M.; Horcajo, P.; Jiménez-Meléndez, A.; Lara, P.A.; Huertas-López, A.; Huertas-López, F.; Ferre, I.; Ortega-Mora, L.M.; Álvarez-García, G. Transcriptomics of Besnoitia besnoiti-Infected Fibroblasts Reveals Hallmarks of Early Fibrosis and Cancer Progression. Microorganisms 2024, 12, 586. https://doi.org/ 10.3390/microorganisms12030586
NO Author contributions: G.Á.-G., I.F. and L.M.O.-M. conceived the study and acquired funding for the study; M.F.-Á., A.J.-M. and P.H. carried out the experimental assays; M.F.-Á., P.A.L., A.H.-L. and F.H.-L. performed the bioinformatic and statistical analyses and prepared the figures and tables. M.F.-Á., G.Á.-G. and P.H. drafted the original manuscript. All authors have read and agreed to the published version of the manuscript.
NO Spanish Ministry of Economy and Competitiveness
NO Community of Madrid
NO Complutense University of Madrid
NO University of Murcia through the Margarita Salas Program of Requalification of the Spanish University System (Spanish Ministry of Universities) financed by the European Union—NextGenerationEU
DS Docta Complutense
RD 28 abr 2025