The non-alcoholic fatty liver disease (NAFLD) is rapidly expanding worldwide as its incidence is correlated with the obesity pandemic. NAFLD encompasses a spectrum of pathologies ranging from simple steatosis characterized by triglyceride (TG) accumulation in hepatocytes, to non-alcoholic steatohepatitis (NASH) that can progress in some cases to fibrosis, cirrhosis and hepato-cellular carcinoma. In addition to TG accumulation in hepatocytes, NASH is also characterized by hepatic inflammation and fibrogenesis. The hepatic fibrogenic process is initiated by the trans-differentiation of quiescent, adipocyte-like hepatic stellate cells (HSC) into myofibroblasts with high energetic requirements, due to their high proliferation rate and specialization into extra-cellular matrix production. Although HSC trans-differentiation is recognized as the cornerstone of the fibrogenic response, the underlying cellular and molecular mechanisms are not fully elucidated yet. We hypothesize that mitochondrial activity plays a key role in HSC trans-differentiation by sustaining the metabolic transition encountered by the cells. The main goals of the MITOSTAR proposal are (i) to assess the changes in mitochondrial activity that occur during trans-differentiation of quiescent HSC into myofibroblasts, (ii) to investigate the potentially mitochondria-mediated role of a new factor identified by Partner 1 in HSC trans-differentiation and subsequent hepatic fibrogenesis (iii) to identify all the mitochondria-related genes that regulate HSC trans-differentiation and fibrogenesis progression. The identification and the dissection of such mechanisms are crucial if we hope to effectively design potential new therapeutic strategies and translate our discoveries to the clinic.
Madame Fabienne FOUFELLE (CENTRE DE RECHERCHE DES CORDELIERS)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
CRC CENTRE DE RECHERCHE DES CORDELIERS
IBGC INSTITUT DE BIOCHIMIE ET GENETIQUE CELLULAIRES
Help of the ANR 438,051 euros
Beginning and duration of the scientific project: December 2019 - 36 Months