Ponente: Dr. Porfirio Nava Domínguez
Procedencia: Departamento de Fisiología Biofísica y Neurociencias
Centro de Investigación y Estudios Avanzados del IPN.


Epithelial cells lining the intestinal tract form a selective barrier that regulates nutrient uptake and limits exposure to luminal antigens and toxins. The intestinal epithelium is highly dynamic and actively turned over. This process requires regulated intestinal stem cell proliferation, differentiation, migration and apoptosis. Accumulating evidence suggests that epithelial barrier properties are compromised in Inflammatory Bowel Disease (IBD). Altered intercellular junction function, micro-erosions and increased epithelial apoptosis have been proposed to contribute to epithelial barrier breakdown during colitis. In animal models, increased paracellular permeability across intestinal epithelial cells has been observed prior to the onset of inflammation and, it has been showed that increased paracellular permeability enhances antigenic exposure to underlying immune cells thereby further compromising epithelial barrier function. Therefore, it is now evident that impaired homeostasis and epithelial barrier disruption are important pathophysiological events in the development of IBD. Intercellular junctions encompassing Tight Junctions (TJs), Adherens Junctions (AJs), and Desmosomes (DMs) play a pivotal role in regulating epithelial barrier properties. My research highlighted the importance of DMs and Akt/β-catenin signaling in regulating intestinal epithelial barrier function and their contribution to the pathophysiology of mucosal inflammation. We demonstrated that proinflammatory cytokines regulate intestinal epithelial homeostasis (proliferation and apoptosis) by inducing hyperactivation of the Akt/β-catenin signaling. Our studies suggest that desmosomal cadherins, proinflammatory cytokines and commensal bacteria can affect PI3K and its downstream proteins PTEN, mTORC2, mTORC1, PDK1, Akt in order to activate and inhibit β-catenin signaling to control epithelial homeostasis. An improved comprehension of the mechanisms involved in controlling this biological process will promote the understanding of the pathophysiological events that leads to epithelial barrier breakdown observed in the mucosa of IBD patients.

Jueves 13 hr
Auditorio del IF