Molecular regulation of inflammatory pathways in human endothelial senescence

• Autores: Renuka kandhaya Pillai
• Directores de la Tesis: Simó Schwartz Navarro (dir. tes.), Francesc Miró Mur (codir. tes.), Jaume Alijotas Reig (codir. tes.), Bru Cormand Rifa (tut. tes.)
• Lectura: En la Universitat de Barcelona ( España ) en 2011
• Idioma: español
• Tribunal Calificador de la Tesis: Daniel Grinberg Vaisman (presid.), Ramon Mangues Bafalluy (secret.), Joan Sayós Ortega (voc.)
• Materias:
  • Química
    • Bioquímica
      • Biología molecular
  • Ciencias de la vida
    • Biología celular
      • Cultivo celular
      • Citogenética
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• Resumen

  • Cellular senescence is a state in which cells lose their ability to proliferate and can be triggered by various stress stimuli including telomere erosion, DNA damage, oncogenic and inflammatory signaling. Inflammation and inflammatory signaling plays a key role in cellular aging, age related diseases and cancer. Role of endothelial cells in inflammation is also crucial since they serve as sensors and transducers of signals. In the present study,we have established an experimental model of senescence using chronic TNF signals and determined the molecular regulation of inflammatory pathways during endothelial senescence. Here, we provide a comprehensive overview of gene expressional changes, novel targets and regulatory pathways involved in contributing to senescence phenotype. By gene expression profiling, we identified the crucial involvement of inflammatory network and interferon signature in TNF-mediated senescence. In Particular, we show that persistence activation of STAT1/3 establishes a positive auto-regulatory loop, which promote sustained inflammatory and interferon signature. In addition, our results also show that repressed replication, defective DNA repair mechanism and misregulated mitotic machinery potentially contribute to the irreversible senescence state