PRE2023-IMPACTO DE LA MATRIZ EXTRACELULAR SOBRE LA BIOLOGIA CELULAR Y LA REPROGRAMACION METABOLICA DE LA FIBROSIS ORGANICA-(PID2022-136703OB-I00)

Fibrosis is defined by scarring and tissue hardening caused by excess deposition of extracellular matrix (ECM) components, mainly collagens. A fibrotic response can occur in any tissue of the body and is the final outcome of an unbalanced reaction to inflammation and wound healing induced by a variety of insults, including persistent infections, autoimmune reactions, allergic responses, chemical exposure, radiation, and tissue injury. The accumulation of ECM proteins replaces the live tissue and disrupts the architecture leading to organ malfunction. Fibrosis is a major clinical and therapeutic challenge and has been estimated to account for 45% of deaths in the developed world. Current treatment options are scarce and ineffective, therefore, there is an urgent need for new pharmacological therapies. Understanding the molecular and cellular connections between ECM stiffness, metabolism and hypoxia can unveil potential mechanisms underlying the development of fibrosis. The present proposal intends to investigate the crosstalk between ECM deposition and stiffness and the cellular responses to hypoxia and metabolic reprogramming. We believe this will provide a solid basis to develop new therapeutic approaches that may halt and eventually revert the process of fibrosis.