Mfap4: a promising target for enhanced liver regeneration and chronic liver disease treatment.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 37935709.
- Also identified by DOI 10.1038/s41536-023-00337-9 and PMC identifier 10630300.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The liver has a remarkable regenerative capacity. Nevertheless, under chronic liver-damaging conditions, this capacity becomes exhausted, allowing the accumulation of fibrotic tissue and leading to end-stage liver disease. Enhancing the endogenous regenerative capacity by targeting regeneration breaks is an innovative therapeutic approach. We set up an in vivo functional genetic screen to identify such regeneration breaks. As the top hit, we identified Microfibril associated protein 4 (Mfap4). Knockdown of Mfap4 in hepatocytes enhances cell proliferation, accelerates liver regeneration, and attenuates chronic liver disease by reducing liver fibrosis. Targeting Mfap4 modulates several liver regeneration-related pathways including mTOR. Our research opens the way to siRNA-based therapeutics to enhance hepatocyte-based liver regeneration.