Identification and functional characterization of an unforeseen novel transcription factor controlling hepatic stellate cell activation and liver fibrosis – HSCreg

Fatty liver diseases among which alcoholic and non-alcoholic steatohepatitis [(N)ASH] have become a major health issue worldwide as they represent a major cause of liver failure and cancer. This is due to liver insult leading to fibrosis, a detrimental excess of extracellular matrix (ECM) deposition. The main contributors to this process are hepatic stellate cells (HSCs) which undergo myofibroblastic activation during (N)ASH development acquiring an uncontrolled ECM protein production phenotype. Despite being of central clinical importance regarding (N)ASH, how HSC activation is orchestrated at the molecular level has remained poorly defined. Bioinformatics analyses have allowed us to identify an unforeseen transcription factor, which drives HSC profibrotic activation. By combining functional genomics, in-vivo mouse models as well as the study of human liver biopsies, our project will allow to define clinically relevant novel molecular mechanisms involved in HSC-driven liver fibrosis.