SOCS2 Balances Metabolic and Restorative Requirements during Liver Regeneration.

Masuzaki R, Zhao S, Valerius MT, Tsugawa D, Oya Y, Ray KC, Karp SJ
J Biol Chem. 2016 291 (7): 3346-58

PMID: 26703468 · PMCID: PMC4751379 · DOI:10.1074/jbc.M115.703264

After significant injury, the liver must maintain homeostasis during the regenerative process. We hypothesized the existence of mechanisms to limit hepatocyte proliferation after injury to maintain metabolic and synthetic function. A screen for candidates revealed suppressor of cytokine signaling 2 (SOCS2), an inhibitor of growth hormone (GH) signaling, was strongly induced after partial hepatectomy. Using genetic deletion and administration of various factors we investigated the role of SOCS2 during liver regeneration. SOCS2 preserves liver function by restraining the first round of hepatocyte proliferation after partial hepatectomy by preventing increases in growth hormone receptor (GHR) via ubiquitination, suppressing GH pathway activity. At later times, SOCS2 enhances hepatocyte proliferation by modulating a decrease in serum insulin-like growth factor 1 (IGF-1) that allows GH release from the pituitary. SOCS2, therefore, plays a dual role in modulating the rate of hepatocyte proliferation. In particular, this is the first demonstration of an endogenous mechanism to limit hepatocyte proliferation after injury.

© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

MeSH Terms (19)

Animals Cell Proliferation Cells, Cultured Gene Expression Regulation Growth Hormone Hepatectomy Immunohistochemistry Insulin-Like Growth Factor I Liver Liver Regeneration Male Mice, Inbred C57BL Mice, Knockout Pituitary Gland Protein Transport Proteolysis Receptors, Somatotropin Suppressor of Cytokine Signaling Proteins Ubiquitination

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