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PMID: 17148669 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Oval cell response in 2-acetylaminofluorene/partial hepatectomy rat is attenuated by short interfering RNA targeted to stromal cell-derived factor-1.

The American journal of pathology ·Vol. 169 ·No. 6 ·2006-12-00 ·Pages 2066-74

Zheng D, Oh SH, Jung Y, Petersen BE

Abstract

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.

MeSH Terms
2-Acetylaminofluorene Animals Animals, Genetically Modified Apoptosis Carcinogens/administration & dosage Cell Count Chemokine CXCL12 Chemokines, CXC/genetics,metabolism,physiology Female Hepatectomy Ki-67 Antigen/analysis Liver/cytology,metabolism RNA, Small Interfering Rats Rats, Inbred F344 Receptors, CXCR4/physiology
Chemicals
Carcinogens Chemokine CXCL12 Chemokines, CXC Cxcr4 protein, rat Ki-67 Antigen RNA, Small Interfering Receptors, CXCR4 2-Acetylaminofluorene
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Zheng Donghang
Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, P.O. Box 100275, Gainesville, FL 32610-0275, USA.
Oh Seh-hoon
Jung Youngmi
Petersen Bryon E
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.2353/ajpath.2006.060211
Published
2006-12-00
Pages
2066-74
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1762488
Subset
IM
Grants
NIDDK NIH HHS · R01 DK065096 · United States
NIDDK NIH HHS · DK058614 · United States
NIDDK NIH HHS · R56 DK058614 · United States
NIDDK NIH HHS · R01 DK058614 · United States
NIDDK NIH HHS · DK065096 · United States
External Links
PubMed source DOI: 10.2353/ajpath.2006.060211 PMC Full Text View journal details
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