Patients with type 2 diabetes mellitus develop more progressive non-alcoholic steatohepatitis (NASH), often leading to liver failure and hepatocellular carcinoma. We are studying how advanced glycation end products (AGEs) are involved in inflammation and fibrosis focusing on NADPH oxidase-mediated redox stress, dysregulated anti-oxidant responses and their link to the activation of stellate cells, and altered matrix dynamics (JCI, 2020). The extracellular matrix (ECM) is a diverse microenvironment that maintains bi-directional communication with cells to regulate tissue homeostasis. AGEs promote ECM crosslinking in a non-enzymatic way, which can influence matrix mechanics and cellular responses in NASH. By collaborating with Bioengineering we are pursuing studies on novel model systems, where the intricate matricellular crosstalks can be investigated.
