Publicação
Unraveling the biological potential of skin fibroblast
| Resumo: | Objective: In this study, we examined the molecular response of human skin fibroblasts to an inflammatory cytokine to evaluate their suitability as models for immunopathology research. Methods: Skin fibroblasts were stimulated with tumour necrosis factor (TNF)-α, and the transcriptome was profiled via RNA-Seq. The differentially expressed genes were screened to predict immunological pathways and interactions. The cytokines and signaling pathways were validated at protein level. Similarly to immune cells, TNF-α caused transcriptional and transductional changes in fibroblasts. Results: Functional analysis revealed significant enrichment of TNF-α signaling and cell chemotaxis (normalized enrichment score = 2.59 and 3.42). We also detected enrichment of nuclear factor kappa B (NF-κB) target genes and NF-kB activation, confirmed by complete protein degradation of its inhibitor IκBa (p = 0.0019). The MAPK/ERK and p38 MAPK pathways were also activated. Finally, we observed significant secretion of proinflammatory cytokines and chemokines, such as interleukin 6 (p = 0.02), CXCL8 (p = 0.027), CCL2 (p = 0.028) and CCL5 (p = 0.016). Conclusion: This study advances the biological understanding of skin fibroblast responses to TNF-α, revealing their intracellular pathways and secretome. It discloses techniques for leveraging fibroblasts' potential as in vitro models to identify inflammatory drivers, particularly when alternative models are inaccessible. |
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| Autores principais: | Pascoal, Carlota |
| Outros Autores: | Granjo, Pedro; Mexia, Patrícia; Gallego, Diana; Lourenço, Rita Adubeiro; Sharma, Shally; Pérez, Bélen; Castro-Caldas, Margarida; Grosso, Ana Rita; Ferreira, Vanessa dos Reis; Videira, Paula Alexandra |
| Assunto: | Fibroblasts Immune response Inflammation Transcriptome Tumour necrosis factor-alpha Immunology and Allergy Immunology |
| Ano: | 2025 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade Nova de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Institucional da UNL |
| Resumo: | Objective: In this study, we examined the molecular response of human skin fibroblasts to an inflammatory cytokine to evaluate their suitability as models for immunopathology research. Methods: Skin fibroblasts were stimulated with tumour necrosis factor (TNF)-α, and the transcriptome was profiled via RNA-Seq. The differentially expressed genes were screened to predict immunological pathways and interactions. The cytokines and signaling pathways were validated at protein level. Similarly to immune cells, TNF-α caused transcriptional and transductional changes in fibroblasts. Results: Functional analysis revealed significant enrichment of TNF-α signaling and cell chemotaxis (normalized enrichment score = 2.59 and 3.42). We also detected enrichment of nuclear factor kappa B (NF-κB) target genes and NF-kB activation, confirmed by complete protein degradation of its inhibitor IκBa (p = 0.0019). The MAPK/ERK and p38 MAPK pathways were also activated. Finally, we observed significant secretion of proinflammatory cytokines and chemokines, such as interleukin 6 (p = 0.02), CXCL8 (p = 0.027), CCL2 (p = 0.028) and CCL5 (p = 0.016). Conclusion: This study advances the biological understanding of skin fibroblast responses to TNF-α, revealing their intracellular pathways and secretome. It discloses techniques for leveraging fibroblasts' potential as in vitro models to identify inflammatory drivers, particularly when alternative models are inaccessible. |
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