Celiac disease (CD) is a common heritable autoimmune disorder triggered by gluten-containing cereals which induce a massive immune reaction and destruction of the small bowel mucosa. The disease is hallmarked by the production of antibodies against transglutaminase 2 (TG2), an enzyme involved in angiogenesis. Interestingly CD presents an entire disorganization of the intestinal vasculature where the TG2 autoantibodies are deposited. We recently demonstrated that anti-TG2 antibodies can disrupt and affect the vascular functionality in vitro. Therefore we aimed to study whether antibodies against TG2 can affect vasculature in vivo by increasing TG2 enzymatic activity affecting the extracellular matrix composition and signaling intracellularly. In addition, the inhibition of TG2 enzymatic activity and other molecular pathways can ameliorate the anti-angiogenic effect of CD autoantibodies, offering a potential therapeutical target ordered by the primary users of our study, patients. The results find of the present project will be a step forward in the knowledge of the disease and the pathogenic mechanisms especially those related with the vascular development. To achieve this question, different models of angiogenesis and other molecular methods will be used. Multidisciplinarity is the main strength of the present research combining the knowledge of different fields (molecular biology, clinical observations) as well many collaborations with other researchers and companies. Applicant will contribute with his knowledge about angiogenesis and inflammation while host institution provided the experience in celiac disease research as well the facilities need it making the project feasible. The amount apply is 15,000 € year during 36 month (total 45,000€) to cover consumables, travel and other costs. The present reintegration grant will have a very big impact on applicant future career giving him the possibility to incorporate as a docent in his host organization.
Field of science
- /natural sciences/biological sciences/molecular biology
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