Oval cell response in 2-acetylaminofluorene/partial hepatectomy rat is attenuated by short interfering RNA targeted to stromal cell-derived factor-1.
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.
Zheng
Donghang
D
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
SH
Jung
Youngmi
Y
Petersen
Bryon E
BE
D015073:2-Acetylaminofluorene; D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis; D002273:Carcinogens / Q000008:administration & dosage; D002452:Cell Count; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D005260:Female; D006498:Hepatectomy; D019394:Ki-67 Antigen / Q000032:analysis; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D034741:RNA, Small Interfering; D051381:Rats; D011916:Rats, Inbred F344; D019718:Receptors, CXCR4 / Q000502:physiology*
D002273:Carcinogens; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C486264:Cxcr4 protein, rat; D019394:Ki-67 Antigen; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4; D015073:2-Acetylaminofluorene