Evaluation of the role of the interaction between FAK and Shp2 in the modulation of ibuprofen-induced tissue damage mechanisms in intestinal organoids.

• Grant number: 25/11060-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2025
• End date: August 31, 2026
• Field of knowledge: Biological Sciences - Morphology - Histology
• Principal Investigator: Talita Miguel Marin
• Grantee: Gabriela Eliz Ferreira D'Eugenio
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The use of medications can pose risks to human health. Nonsteroidal anti-inflammatory drugs (NSAIDs) increase the likelihood of mucosal lesions, bleeding, and perforation in the lower gastrointestinal tract (GIT), which can lead to impaired nutrient absorption and potentially life-threatening anemia. The molecular processes underlying the morphological and biochemical changes induced by NSAIDs in the GIT are not fully understood. Focal Adhesion Kinase (FAK) is an important regulator of epithelial injury repair, while the protein tyrosine phosphatase Shp2 is involved in the exacerbation of inflammation in the GIT. These proteins may serve as potential modulators of intestinal tissue injury and repair mechanisms. Conventional in vitro and in vivo methods have predictive limitations and often fail to fully emulate human physiology.Therefore, more predictive and cost-effective tests are necessary for successful scientific investigations, particularly those related to human diseases, drug discovery, and development. In vitro models, such as artificial equivalents of human organs or organoids, offer an alternative that can enhance predictive power. These models can better replicate the histoarchitecture and in vivo environment, which is essential for obtaining physiologically relevant responses. Intestinal organoids that closely resemble the human intestinal epithelium, including its response to pharmacological exposure, will be valuable in investigating new mechanisms involved in the adverse effects of the NSAID ibuprofen. We have previously demonstrated that Shp2 directly associates with FAK both in vitro and in vivo, negatively modulating its activity. This project aims to evaluate the roles of FAK and Shp2 in the onset and maintenance of injury caused by exposure to ibuprofen in human intestinal organoids. (AU)