Hepatic expression of cell proliferation markers and growth factors in giant cell hepatitis: implications for the pathogenetic mechanisms involved.
Hepatic expression of cell proliferation markers and growth factors in giant cell hepatitis: implications for the pathogenetic mechanisms involved.
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巨细胞肝炎中细胞增殖标志物和生长因子的肝脏表达：对相关发病机制的影响。
DOI：
10.1097/mpg.0b013e3181f85a87
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发表时间：
2011
影响因子：
2.9
通讯作者：
Lau,JohnsonYN
中科院分区：
文献类型：
--
作者：
Fang,JaneWS;Gonzalez-Peralta,ReginoP;Chong,SonnyKF;Lau,GraceM;Lau,GillianM;Lau,JohnsonYN
目的：本研究的目的是确定巨细胞肝炎（GCH）中巨细胞（GCs）的形成是否与无丝分裂或核扩散有关。患者和方法：对18例特发性婴儿期GCH患儿和12例婴儿期后GCH患儿的肝脏切片进行增殖细胞核抗原（PCNA）、人组蛋白3 (H3) mRNA、转化生长因子α (TGF-α)、TGF-β1、肝细胞生长因子（HGF）、表皮生长因子受体（EGFR）的表达测定。结果：18例婴儿GCH活检中有10例（56%）和12例婴儿GCH后活检中有11例（92%）在GC和非GC肝细胞核中检测到1%至80%的增殖标志物，但在正常肝脏中未检测到增殖标志物。增殖标志物在gc肝细胞中的表达与非gc肝细胞相似（P< 0.05）。TGF-α和EGFR在GCs（9/29和4/30婴儿期或婴儿期后GCH患者）和非gc肝细胞（15/29和11/30婴儿期或婴儿期后GCH患者）中均检测到。29例患儿中有20例、30例患儿中有10例患儿的窦细胞中主要检测到TGF-β1和HGF；HGF与非gc型肝细胞PCNA、H3 mRNA及gc型肝细胞H3 mRNA表达呈正相关（P< 0.01）。结论：婴儿期和婴儿期后GCH患者肝脏中增殖标志物和生长因子表达相似，ggc和非gc肝细胞中均检测到增殖标志物的比例较高，HGF的表达与增殖标志物呈正相关。这些数据表明，至少在一部分GCH患者中，核扩散可能促进了GCs的发病机制。本文提出了GCH的发病机制模型。
Objectives:The aim of this study is to determine whether amitotic division or nuclear proliferation is involved in the formation of giant cells (GCs) in giant cell hepatitis (GCH).Patients and Methods:Liver sections from 18 pediatric patients with idiopathic infantile GCH and 12 patients with postinfantile GCH were evaluated for the expression of proliferating cell nuclear antigen (PCNA) and human histone 3 (H3) mRNA, transforming growth factor-alpha (TGF-α), TGF-β1, hepatocyte growth factor (HGF), and epidermal growth factor receptor (EGFR).Results:Proliferation markers were detected in 1% to 80% in the nuclei of GC and non-GC hepatocytes in 10 of 18 (56%) infantile GCH biopsies and 11 of 12 (92%) postinfantile GCH biopsies, but not in normal liver. The expression of proliferation markers in GCs paralleled that in non-GC hepatocytes (P< 0.05 for both markers). TGF-α and EGFR were detected in both GCs (9/29 and 4/30 patients with infantile or postinfantile GCH, respectively) and non-GC hepatocytes (15/29 and 11/30 patients with infantile or postinfantile GCH, respectively). TGF-β1 and HGF were detected mainly in sinusoidal cells in 20 of 29 and 10 of 30 patients with infantile or postinfantile GCH, respectively; the expression of HGF was positively correlated with PCNA and H3 mRNA in non-GC hepatocytes and with H3 mRNA in GCs (P< 0.01).Conclusions:Hepatic expressions of nuclear proliferation markers and growth factors were similar in infantile and postinfantile GCH, nuclear proliferation markers were detected in both GCs and non-GC hepatocytes in a high proportion of patients, and expression of HGF correlated positively with the proliferation markers. These data indicate that nuclear proliferation may contribute to the pathogenesis of GCs in at least a proportion of patients with GCH. A model for the pathogenesis of GCH is proposed.