Modulation of liver regeneration via myeloid PTEN deficiency

Wen Tao Ma, Yan Jie Jia, Qing Zhi Liu, Yan Qing Yang, Jing Bo Yang, Zhi Bin Zhao, Zhen Ye Yang, Qing Hua Shi, Hong Di Ma, M. Eric Gershwin, Zhe Xiong Lian

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Abstract

Molecular mechanisms that modulate liver regeneration are of critical importance for a number of hepatic disorders. Kupffer cells and natural killer (NK) cells are two cell subsets indispensable for liver regeneration. We have focused on these two populations and, in particular, the interplay between them. Importantly, we demonstrate that deletion of the myeloid phosphatase and tensin homolog on chromosome 10 (PTEN) leading to an M2-like polarization of Kupffer cells, which results in decreased activation of NK cells. In addition, PTEN-deficient Kupffer cells secrete additional factors that facilitate the proliferation of hepatocytes. In conclusion, PTEN is critical for inhibiting M2-like polarization of Kupffer cells after partial hepatectomy, resulting in NK cell activation and thus the inhibition of liver regeneration. Furthermore, PTEN reduces growth factor secretion by Kupffer cells. Our results suggest that targeting PTEN on Kupffer cells may be useful in altering liver regeneration in patients undergoing liver resection.

Original languageEnglish (US)
Pages (from-to)e2827
JournalCell death & disease
Volume8
Issue number5
DOIs
StatePublished - May 25 2017

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ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Cite this

Ma, W. T., Jia, Y. J., Liu, Q. Z., Yang, Y. Q., Yang, J. B., Zhao, Z. B., Yang, Z. Y., Shi, Q. H., Ma, H. D., Gershwin, M. E., & Lian, Z. X. (2017). Modulation of liver regeneration via myeloid PTEN deficiency. Cell death & disease, 8(5), e2827. https://doi.org/10.1038/cddis.2017.47