MODULATION OF KERATIN-14 AND ALPHA-FETOPROTEIN EXPRESSION DURING HEPATIC OVAL CELL-PROLIFERATION AND LIVER-REGENERATION
MODULATION OF KERATIN-14 AND ALPHA-FETOPROTEIN EXPRESSION DURING HEPATIC OVAL CELL-PROLIFERATION AND LIVER-REGENERATION
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DOI：
10.1002/jcp.1041590312
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发表时间：
1994-06-01
影响因子：
5.6
通讯作者：
THORGEIRSSON, SS
中科院分区：
文献类型：
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作者：
BISGAARD, HC;NAGY, P;THORGEIRSSON, SS
角蛋白14（K14）表达最近已在非实质肝来源的细胞系中得到证实（Bisgaard等人，1993年梅尔巨蟹座，7：60-66; Bisgaard等人，1991，J. Cell.生理学，747：333-343）。这些细胞系被认为代表了成年大鼠肝脏中存在的休眠干细胞区室的后代，其可能参与实验性肝损伤后肝脏质量的恢复。利用2-乙酰氨基芴（2-AAF）管理和部分肝切除术的组合，以激活肝再生的卵圆细胞增殖，我们研究了调制K14以及甲胎蛋白（AFP）的表达在增殖的卵圆细胞和谱系假设是从这里派生。我们通过北方印迹和原位杂交分析表明，K14和AFP转录本最初积累在位于汇管区导管结构亚群的上皮细胞中。随着卵圆细胞浸润肝实质，在卵圆细胞、小嗜碱性肝细胞灶和类似腺泡型上皮的结构中检测到K14转录本。AFP在卵圆细胞中表达，在嗜碱性肝细胞灶中表达较低但可检测到，但在腺泡型上皮中不表达。无论是K14还是AFP转录检测胆管或成熟肝细胞在任何时间在卵圆细胞增殖和重建的肝脏质量。为了进一步研究K14和AFP表达的调节，我们利用体外模型，其中大鼠肝上皮（RLE）细胞的自发转化似乎模仿体内沿肝谱系沿着的早期分化过程。我们证明，未分化的RLE细胞在后期传代表达K14和波形蛋白，而转化和分化成肝细胞样后代导致废除K14和波形蛋白的表达和K18和AFP的诱导。我们建议，K14和AFP依次调制的卵圆细胞亚群参与正在进行的重建肝脏质量。(C)1994 Wiley-Liss，Inc.
Keratin 14 (K14) expression has recently been demonstrated in cell lines of nonparenchymal hepatic origin (Bisgaard et al., 1993, Mel. Carcinog., 7:60-66; Bisgaard et al., 1991, J. Cell. Physiol., 747:333-343). These cell lines are thought to represent a progeny of a dormant stem cell compartment present in the adult rat liver, which may participate in the restoration of the liver mass after experimental liver injury. Utilizing a combination of 2-acetylaminofluorene (2-AAF) administration and partial hepatectomy to activate liver regeneration by proliferation of oval cells, we examined the modulation of K14 as well as alpha-fetoprotein (AFP) expression in proliferating oval cells and lineages hypothesized to be derived here from. We showed by Northern blot and in situ hybridization analyses that K14 and AFP transcripts were initially accumulating in epithelial cells located in subsets of ductal structures in the portal areas. As oval cells infiltrated the liver parenchyma, K14 transcripts were detected in oval cells, in foci of small basophilic hepatocytes, and in structures resembling glandular intestinal-type epithelium. AFP was expressed in oval cells, and at low but detectable levels in foci of basophilic hepatocytes, but not in glandular intestinal-type epithelium. Neither K14 nor AFP transcripts were detected in bile ducts or mature hepatocytes at any time during oval cell proliferation and reconstitution of the liver mass. To further study the modulation of K14 and AFP expression we utilized an in vitro model in which spontaneous transformation of rat liver epithelial (RLE) cells appeared to mimic the process of early differentiation along the hepatic lineage in vivo. We demonstrated that undifferentiated RLE cells at a late passage expressed K14 and vimentin, whereas transformation and differentiation to hepatoblast-like progeny resulted in an abrogation of K14 and vimentin expression and an induction of K18 and AFP. We propose that K14 and AFP are sequentially modulated in subpopulations of oval cells involved in the ongoing reconstitution of the liver mass. (C) 1994 Wiley-Liss, Inc.