Project title

Targeting microRNA-34, a Potential Link between Apoptosis and Nonalcoholic Fatty Liver Disease Pathogenesis

Scientific Coordinator's name:

Rui Eduardo Mota Castro

Scientific Coordinator's e-mail:

ruieduardocastro@ff.ul.pt

Principal R&D Unit:

iMed.UL/FFUL

Other R&D Units involved in the project:

Molecular Medicine Institute (IMM/FM/UL); Department of Medicine and Genetics, Cell Biology and Development, University of Minnesota Medical School (UM)

Project keyword(s)

microRNA-34a; apoptosis; non-alcoholic fatty liver disease (NAFLD); ursodeoxycholic acid (UDCA)

Short abstract and comments

There is still no established, evidence-based treatment for patients with NAFLD and the biological mechanisms underlying the occurrence of steatosis and its progression to non-alchoholic steatohepatitis (NASH) are not entirely known. We hypothesize that specific miRNAs regulate hepatocyte apoptotic pathways involved in NAFLD pathogenesis, and are modulated by UDCA. In particular, this project aims to fully evaluate the interplay between miRNA-34 and apoptosis during NAFLD progression, as well as their modulation by UDCA, which appears to have a significant, but still not fully characterized antiapoptotic and cytoprotective effect in NAFLD.

Potential uses/indications

The identification and characterization of miRNA-34 as an active, determinant player in inducing apoptosis during progression from simple steatosis to NASH in NAFLD, as well as its modulation by UDCA, will embody new molecular targets that can potentially become the object of therapeutic interventions. Ultimately, it may enable us to inhibit the progression of NAFLD to hepatocellular carcinoma or liver failure.