[en] In this work, we have analyzed whether mitochondrial dysfunction in mesothelial cells of the peritoneal membrane, through an increase in the level of oxidative stress and inflammatory mediators, participates in the epithelial-to-mesenchymal transition (EMT) that these cells may undergo in patients treated with peritoneal dialysis (PD). First, ex vivo studies demonstrated that there was a correlation between mitochondrial dysfunction and the EMT status of mesothelial cells, as well as with the time in PD. Furthermore, a positive correlation was evidenced between the free mtDNA in the dialysate, which acts as an indicator of acute mitochondrial damage, and the dialytic function of the peritoneum. Secondly, both the dialysis fluid (DF) and the inflammatory cytokine IL-1ß were described in vitro as having the ability to induce mitochondrial dysfunction in mesothelial cells. This mitochondrial dysfunction increased the expression of the inflammatory mediators COX-2 and IL-8, and the sensitivity of mesothelial cells to inflammatory cytokines. Also, we determined that mitochondrial reactive oxygen species (ROS) and the NF-κB factor were involved in this process. Likewise, mitochondrial ROS were identified as mediators of the EMT process. Finally, it was shown in vitro that natural polyphenol resveratrol protects the mitochondrial function of mesothelial cells, and that it was able to prevent the effects of this dysfunction, positioning it as a potential therapy to preserve the dialytic capacity of the peritoneum during PD treatment. These results could help a better understanding of the pathogenic mechanisms that lead to ultrafiltration failure in PD patients by showing the involvement of the mitochondria in the pathophysiology of the peritoneal membrane.

[gl] Neste traballo evaluouse se a disfunción mitocondrial nas células mesoteliais da membrana peritoneal, a través dun aumento no nivel de estrés oxidativo e dos mediadores inflamatorios, participa na transición epitelio-mesenquimal (TEM) que poden sufrir estas células en pacientes tratados con diálise peritoneal (DP). En primeiro lugar, os estudos ex vivo demostraron que existía unha relación entre a disfunción mitocondrial e o estado de TEM das células mesoteliais, así como co tempo en DP. Ademais, evidenciouse unha correlación positiva entre o ADNmt libre no dializado, que actúa coma un indicador do dano mitocondrial agudo, e a función dialítica do peritoneo. En segundo lugar, describiuse in vitro que tanto o líquido de diálise (LD) como a citocina inflamatoria IL-1ß teñen a capacidade de inducir disfunción mitocondrial nas células mesoteliais. Esta disfunción mitocondrial incrementou a expresión dos mediadores inflamatorios COX-2 e IL-8 e aumentou a sensibilidade das células mesoteliais ás citocinas inflamatorias, determinándose que as especies reactivas de osíxeno (ROS) mitocondriais e o factor NF-κB estaban implicados neste proceso. Así mesmo, identificouse aos ROS mitocondriais como mediadores do proceso de TEM. Finalmente, mostrouse in vitro que o polifenol natural resveratrol protexe a función mitocondrial das células mesoteliais, e que foi capaz de previr os efectos desta disfunción, posicionándoo como unha terapia potencial para preservar a capacidade dialítica do peritoneo durante o tratamento con DP. Estes resultados poderían axudar a unha mellor comprensión dos mecanismos patoxénicos que conducen a un fallo de ultrafiltración nos pacientes en DP ao evidenciar a implicación da mitocondria na fisiopatoloxía da membrana peritoneal.