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Loss of integrin β1 impairs liver regeneration and HCC progression

Nature Reviews Gastroenterology & Hepatology volume 11, page 392 (2014)Cite this article

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Nanoparticles optimised for liver-specific delivery of integrin β1 (Itgb1) siRNA reveal that loss of Itgb1 impairs hepatocyte survival and proliferation after liver injury. In addition, progression of hepatocellular carcinoma (HCC) is retarded after Itgb1 loss owing to decreased proliferation and increased apoptosis of tumour cells.

Although integrins are known to have an important role in highly proliferative cells, little was known about their function in quiescent or slowly proliferating organs. In the first of two complementary papers published in Nature Communications, Speicher et al. compared phenotypes of short-term loss of Itgb1 by using a traditional inducible knockout approach and also via lipid-based nanoparticles for targeting Itgb1 siRNA to the liver. Mice in both groups were subject to partial hepatectomy and harvested 48 h later. A phenotype of substantial necrosis with strongly impaired hepatocyte proliferation occurred in both groups due to suppressed hyperproliferation and elevated apoptosis. The siRNA approach conferred a milder phenotype with no associated mortality (47% of Itgb1 knockout mice died 24–48 h after partial hepatectomy).

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References

  1. Speicher, T. et al. Knockdown and knockout of β1-integrin in hepatocytes impairs liver regeneration through inhibition of growth factor signalling. Nat. Commun. 10.1038/ncomms4862

  2. Bogorad, R. L. et al. Nanoparticle-formulated siRNA targeting integrins inhibits hepatocellular carcinoma progression in mice. Nat. Commun. 10.1038/ncomms4869

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  1. Gillian Patman
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Patman, G. Loss of integrin β1 impairs liver regeneration and HCC progression. Nat Rev Gastroenterol Hepatol 11, 392 (2014). https://doi.org/10.1038/nrgastro.2014.83

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