Stem cell factor restores hepatocyte proliferation in IL-6 knockout mice following 70% hepatectomy
Xiaodan Ren, Cory Hogaboam, Audra Carpenter, Lisa Colletti
Xiaodan Ren, Cory Hogaboam, Audra Carpenter, Lisa Colletti
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Article Hepatology

Stem cell factor restores hepatocyte proliferation in IL-6 knockout mice following 70% hepatectomy

Abstract

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.

Authors

Xiaodan Ren, Cory Hogaboam, Audra Carpenter, Lisa Colletti

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In vitro primary mouse hepatocyte SCF production in response to IL-6. Pr...
In vitro primary mouse hepatocyte SCF production in response to IL-6. Primary mouse hepatocytes were stimulated with 20 ng/ml IL-6 or media alone. Supernatants and supernatants plus cells were harvested at various timepoints and SCF levels were measured by ELISA. Supernatant SCF levels were used to determine levels of soluble SCF. For quantitation of soluble + bound SCF, supernatants plus cells were sonicated and SCF levels in this solution were measured as an estimate of soluble + bound SCF. There were no significant differences noted in levels of soluble compared with soluble + bound SCF in cells incubated in media alone. There were significant increases in soluble SCF levels at all timepoints from cells treated with IL-6 (#P < 0.05 vs. media alone). In addition, levels of soluble + bound SCF were significantly increased after IL-6 treatment compared with treatment with media alone (*P < 0.01 vs. media alone). Furthermore, levels of soluble plus bound SCF were significantly increased compared with levels of soluble SCF alone after IL-6 treatment at all timepoints (†P < 0.05 vs. soluble levels). Data are expressed as the mean ± SEM. Thin line, cells incubated with media alone and assayed for soluble SCF; heavy line, cells incubated with media alone and assayed for soluble and bound SCF; open circles, cells stimulated with IL-6 (20 ng/ml) and assayed for soluble SCF; closed circles, cells stimulated with IL-6 (20 ng/ml) and assayed for soluble plus bound SCF.