Stem cell factor restores hepatocyte proliferation in IL-6 knockout mice following 70% hepatectomy.
Stem cell factor (SCF) is a molecule with known proliferative effects on hematopoietic cells. More recent studies suggest that this molecule may also have effects on cellular differentiation and proliferation in other types of cells. The current investigations demonstrate that there is a large reservoir of SCF in the liver, that hepatic SCF levels change dramatically following partial hepatectomy in mice, and that SCF blockade, either by administration of anti-SCF antibodies or by using genetically altered, SCF-deficient mice, inhibits hepatocyte proliferation after partial hepatectomy; if SCF is replaced in the genetically SCF-deficient mice after partial hepatectomy, hepatocyte proliferation is restored to that seen in WT animals. Furthermore, SCF administration to IL-6 knockout mice also restores hepatocyte proliferation to normal. In vitro studies using primary mouse hepatocytes demonstrate that SCF causes hepatocyte proliferation and is induced by IL-6 and that treatment with anti-SCF antibodies inhibits IL-6-induced hepatocyte proliferation. Further in vivo studies in IL-6 knockout mice demonstrate that SCF administration to these animals increases p-stat3 levels, suggesting that the SCF-induced increase in hepatocyte proliferation in this system is stat3-mediated.
Department of Surgery, University of Michigan, Medical School, Ann Arbor, Michigan 48109-0331, USA. colletti@umich.edu
Xiaodan
X
Ren
Cory
C
Hogaboam
Audra
A
Carpenter
Lisa
L
Colletti
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000502:physiology; D006498:Hepatectomy; D022781:Hepatocytes / Q000502:physiology*; D015850:Interleukin-6 / Q000502:physiology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D050796:STAT3 Transcription Factor; D019089:Stem Cell Factor / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology
D004268:DNA-Binding Proteins; D015850:Interleukin-6; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D019089:Stem Cell Factor; D015534:Trans-Activators; D001973:Bromodeoxyuridine