Keratini in znižanje celične adhezije: posledice za krhkost epitelija pri kroničnem vnetju črevesja (Slovene)

We have provided evidence in favour of two hypotheses. First, keratin gene mutations not cause a down-regulation in cell junction proteins, but also in their distribution, and this does reflect also on the function of simple epithelial keratins K8/K18. We have demonstrated for the first time that K8/K18 mutations do affect paracellular transport and can induce an increase in ”cell leakage” through tight junction destabilization. Second, we have demonstrated that severe keratin mutants have another joint characteristic, which is a lower sensibility to apoptosis inducing ligands, such as TNF and TRAIL. These data demonstrate that cells carrying keratin gene mutations suffer from a number of physiological changes, which on one hand are compensational mechanisms that function to promote cell survival, proliferation and wound healing (in terms of tissue fragiltiy disorders), while on the other are a step closer towards epithelial-mesenchymal transformation and tumor genesis. These findings are original and of great importance for the development of basic science in this field of research.

through our research and by presenting our work at international meetings in the EU and USA we have also advertised Slovenia and Slovenian science. We have many international collaborators and we are part of a privileged number of top labs in the world in this field. Further development is possible, but it demands much higher investments into research and development than there are at the moment.