Zheng Donghang, Oh Seh-hoon, Jung Youngmi, Petersen Bryon E
Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida, P.O. Box 100275, Gainesville, FL 32610-0275, USA.
Am J Pathol. 2006 Dec;169(6):2066-74. doi: 10.2353/ajpath.2006.060211.
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.
已知基质细胞衍生因子-1（SDF-1）在干细胞/祖细胞转运的调节中起关键作用。在肝干细胞（即卵圆细胞）激活过程中，据报道肝脏内SDF-1表达上调，这暗示其在卵圆细胞辅助肝脏再生中可能发挥作用。在本研究中，使用重组腺病毒递送的小干扰RNA敲低了经2-乙酰氨基芴/部分肝切除术处理的大鼠肝脏中的SDF-1表达。这些动物的卵圆细胞反应受到损害，OV6阳性卵圆细胞数量减少证明了这一点。此外，SDF-1表达的敲低导致甲胎蛋白表达显著降低，这意味着这些动物的卵圆细胞激活受损。末端脱氧核苷酸转移酶介导的dUTP缺口末端标记分析显示与SDF-1抑制无关的显著凋亡。相反，如Ki67免疫组织化学所示，SDF-1的抑制导致肝细胞增殖减少，这意味着这些动物的修复过程受到抑制。这些结果表明，SDF-1是卵圆细胞激活所需的必需分子。
