2. Academic Validation
  3. Mfap4: a promising target for enhanced liver regeneration and chronic liver disease treatment

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

  • NPJ Regen Med. 2023 Nov 7;8(1):63. doi: 10.1038/s41536-023-00337-9.
Viktoriia Iakovleva # 1 2 3,  Anna Wuestefeld # 1,  Agnes Bee Leng Ong 1,  Rong Gao 1,  Neslihan Arife Kaya 4,  May Yin Lee 4,  Weiwei Zhai 5 6,  Wai Leong Tam 4 3,  Yock Young Dan 2 7,  Torsten Wuestefeld 8 9 10
Affiliations

Affiliations

  • 1 Laboratory of In Vivo Genetics and Gene Therapy, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Singapore, 138672, Republic of Singapore.
  • 2 Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Republic of Singapore.
  • 3 Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Republic of Singapore.
  • 4 Laboratory of Translational Cancer Biology, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Singapore, 138672, Republic of Singapore.
  • 5 Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, 100101, Beijing, China.
  • 6 Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, 650223, China.
  • 7 Division of Gastroenterology and Hepatology, National University Health System, Singapore, 119074, Republic of Singapore.
  • 8 Laboratory of In Vivo Genetics and Gene Therapy, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), 60 Biopolis Street, Singapore, 138672, Republic of Singapore. [email protected].
  • 9 School of Biological Science, Nanyang University of Singapore, Singapore, 637551, Republic of Singapore. [email protected].
  • 10 National Cancer Centre, Singapore, 169610, Republic of Singapore. [email protected].
  • # Contributed equally.
PMID: 37935709 DOI: 10.1038/s41536-023-00337-9
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.

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