Mfap4: a promising target for enhanced liver regeneration and chronic liver disease treatment

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 brea...

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Bibliographic Details
Published innpj Regenerative medicine Vol. 8; no. 1; p. 63
Main Authors Iakovleva, Viktoriia, Wuestefeld, Anna, Ong, Agnes Bee Leng, Gao, Rong, Kaya, Neslihan Arife, Lee, May Yin, Zhai, Weiwei, Tam, Wai Leong, Dan, Yock Young, Wuestefeld, Torsten
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 07.11.2023
Nature Publishing Group
Nature Portfolio
Subjects
631/337/505
692/699/1503/1607/1605
692/699/1503/1607/2750
Biomaterials
Biomedical and Life Sciences
Biomedicine
Cancer therapies
Cell Biology
Cell cycle
Cell division
Genetics
Genomes
Growth factors
Hepatitis
Immunology
Liver diseases
Regenerative medicine
Regenerative Medicine/Tissue Engineering
Science
Stem Cells
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Summary: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.
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ISSN:2057-3995
2057-3995
DOI:10.1038/s41536-023-00337-9