Identification of myeloid-derived growth factor as a mechanically-induced, growth-promoting angiocrine signal for human hepatocytes

Nat Commun. 2024 Feb 5;15(1):1076. doi: 10.1038/s41467-024-44760-y.


Recently, we have shown that after partial hepatectomy (PHx), an increased hepatic blood flow initiates liver growth in mice by vasodilation and mechanically-triggered release of angiocrine signals. Here, we use mass spectrometry to identify a mechanically-induced angiocrine signal in human hepatic endothelial cells, that is, myeloid-derived growth factor (MYDGF). We show that it induces proliferation and promotes survival of primary human hepatocytes derived from different donors in two-dimensional cell culture, via activation of mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3). MYDGF also enhances proliferation of human hepatocytes in three-dimensional organoids. In vivo, genetic deletion of MYDGF decreases hepatocyte proliferation in the regenerating mouse liver after PHx; conversely, adeno-associated viral delivery of MYDGF increases hepatocyte proliferation and MAPK signaling after PHx. We conclude that MYDGF represents a mechanically-induced angiocrine signal and that it triggers growth of, and provides protection to, primary mouse and human hepatocytes.

MeSH terms

  • Animals
  • Cell Proliferation
  • Endothelial Cells* / metabolism
  • Hepatectomy
  • Hepatocytes / metabolism
  • Humans
  • Interleukins* / metabolism
  • Liver / metabolism
  • Liver Regeneration* / physiology
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism


  • Mitogen-Activated Protein Kinases
  • MYDGF protein, human
  • Interleukins