Expression of hepatocyte growth factor, transforming growth factor α, and transforming growth factor β 1 messenger RNA in various human liver diseases and correlation with hepatocyte proliferation
Expression of hepatocyte growth factor, transforming growth factor α, and transforming growth factor β 1 messenger RNA in various human liver diseases and correlation with hepatocyte proliferation
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DOI：
10.1002/hep.510240207
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发表时间：
1996-08
期刊：
影响因子：
13.5
通讯作者：
M. Masuhara;M. Yasunaga;K. Tanigawa;F. Tamura;S. Yamashita;I. Sakaida;K. Okita
中科院分区：
文献类型：
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作者：
M. Masuhara;M. Yasunaga;K. Tanigawa;F. Tamura;S. Yamashita;I. Sakaida;K. Okita
肝细胞生长因子（HGF）和转化生长因子α（TGF-α）刺激大鼠的肝再生，而转化生长因子β 1（TGF-β 1）抑制肝再生。然而，它们在人类肝脏疾病，特别是在严重急性肝损伤中的意义仍不清楚。我们使用竞争性逆转录聚合酶链反应研究了肝病患者肝脏中HGF、TGF-α和TGF-β 1信使RNA（mRNA）的表达。从微小的肝活检样品中可以检测到mRNA表达的两倍差异。然后，我们用增殖细胞核抗原（PCNA）染色检查细胞增殖。急性肝炎（AH）患者的HGF mRNA水平显著高于慢性肝病（EX）患者（约3倍）（P <0.05）。TGF-α mRNA水平在AH中显著高于EX（约2倍）（P <0.05），在慢性肝炎（CH）中显著高于EX（约3倍）（P <0.05）。各组TGF-β 1 mRNA水平无显著差异。在急性肝损伤（AH和EX）中，肝组织中HGF mRNA表达与PCNA标记指数（LI）之间存在显著相关性（r = .87，P < .0005）。TGF-α mRNA表达与PCNA指数呈正相关（r = 0.92，P <0.0001）。肝组织PCNA LI与血清HGF无明显相关性。总之，肝脏中产生的HGF和TGF-α刺激肝细胞增殖以响应人类急性肝损伤。
Hepatocyte growth factor (HGF) and transforming growth factor α (TGF‐α) stimulate liver regeneration, whereas transforming growth factor β 1 (TGF‐β 1) inhibits it in rats. However their significance in human liver diseases, especially in severe acute liver injury, remains unclear. We studied HGF, TGF‐α, and TGF‐β 1 messenger RNA (mRNA) expression in the livers of patients with live diseases using a competitive reverse transcriptase polymerase chain reaction. As little as a twofold difference in mRNA expression could be detected from minute liver biopsy samples. We then examined cell proliferation using proliferating cell nuclear antigen (PCNA) staining. HGF mRNA levels were significantly higher (approximately threefold) in acute hepatitis (AH) than in exacerbation of chronic liver disease (EX) (P < .05). TGF‐α mRNA levels were significantly greater in AH (approximately twofold) than EX (P < .05), and the levels were significantly higher (approximately threefold) in chronic hepatitis (CH) than in EX (P < .05). The TGF‐β 1 mRNA levels in all the groups were not significantly different. In acute liver injury (AH and EX), there was a significant correlation between HGF mRNA expression and the PCNA labeling index (LI) in the liver (r = .87, P < .0005). TGF‐α mRNA expression also correlated with the PCNA LI (r = .92, P < .0001). There was no significant correlation between the serum HGF and the PCNA LI in the liver. In conclusion, HGF and TGF‐α produced in the liver stimulate hepatocyte proliferation in response to acute liver injury in humans.