Inhibition of signal transducer and activator transcription factor 3 in rats with acute hepatic failure
2000 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 273, no 1, 129-135 p.Article in journal (Refereed) Published
In fulminant hepatic failure, survival is not possible without recovery of sufficient hepatocyte mass. Remarkably, only a few studies exist that provide insight into the mechanisms that control proliferation of residual hepatocytes after extensive hepatocyte loss. In this regard, the role of growth-regulatory factors, including pro-inflammatory cytokines such as interleukin-6 (IL-6), is not well understood. In the present study we show that in rats with critically low (10%) hepatocyte mass, whether with or without ongoing liver cell necrosis, inhibition of liver regeneration is associated with early and sustained increase in blood IL-6 levels. Under these conditions, the signal transducer and activator of transcription (Stat3) DNA binding activity was lowered at the time of G1/S cell-cycle transition. We further demonstrate that the protein inhibitor of activated Stat3 (PIAS3) and the suppressor of cytokine signaling (SOCS-1) were upregulated early after induction of liver failure (6-12 h), In vitro, IL-6 induced PIAS3 expression in HGF stimulated rat hepatocytes. These findings suggest that after massive hepatocyte loss, an early and rapid rise in blood IL-6 levels may weaken the hepatic regenerative response through up-regulation of Stat3 inhibitors PIAS3 and SOCS-1.
Place, publisher, year, edition, pages
2000. Vol. 273, no 1, 129-135 p.
hepatocyte, hepatic failure, hepatic regeneration, cell growth, signal transduction, transcription factors, hepatectomy
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-141436DOI: 10.1006/bbrc.2000.2881ISI: 000087932800023OAI: oai:DiVA.org:uu-141436DiVA: diva2:385590