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(American Journal of Pathology. 2006;169:2066-2074.)
© 2006 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2006.060211

Oval Cell Response in 2-Acetylaminofluorene/Partial Hepatectomy Rat Is Attenuated by Short Interfering RNA Targeted to Stromal Cell-Derived Factor-1

Donghang Zheng*, Seh-hoon Oh*, Youngmi Jung* and Bryon E. Petersen*{dagger}

From the Department of Pathology, Immunology, and Laboratory Medicine, Program in Stem Cell Biology and Regenerative Medicine,* and the College of Medicine,{dagger} University of Florida, Gainesville, Florida

Stromal cell-derived factor-1 (SDF-1) is known to play an essential role in the regulation of stem/progenitor cell trafficking. During hepatic stem, or oval, cell activation, SDF-1 has been reported to be up-regulated within the liver, implying a possible role in oval cell-aided liver regeneration. In the present study, SDF-1 expression was knocked down in the liver of 2-acetylaminofluorene/partial hepatectomy-treated rats using short interfering RNA delivered by recombinant adenovirus. The oval cell response was compromised in these animals, as evidenced by a decreased number of OV6-positive oval cells. In addition, knockdown of SDF-1 expression caused a dramatic decrease in {alpha}-fetoprotein expression, implying impaired oval cell activation in these animals. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling assay showed no significant apoptosis related to SDF-1 suppression. Instead, as revealed by Ki67 immunohistochemistry, the suppression of SDF-1 resulted in decrease of hepatic cell proliferation, implying the repair process had been inhibited in these animals. These results indicate that SDF-1 is an essential molecule needed in oval cell activation.








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Copyright © 2006 by the American Society for Investigative Pathology.