REGULATION OF HEPATOCYTE GROWTH

肝细胞再生的调节一直被认为是抑制性细胞因子(转化生长因子-β)和促进细胞因子(促转化生长因子)之间的平衡。有报道称，转化生长因子-β的主要产生细胞是星状细胞，星状细胞在肝纤维化中起重要作用。在慢性炎症条件下，再生的肝细胞或星状细胞主要产生的胞外基质将取代坏死组织。NK细胞可能参与了肝细胞再生的调节。本研究的结果如下：(1)每周两次的猪血清处理诱导了肝纤维化，肝组织中转化生长因子-β的表达增加，其中70%的肝切除的转化生长因子-β诱导的肝组织与正常肝相比再生缓慢。(2)胆碱缺乏的饮食诱导的肝硬变和癌前病变中转化生长因子-β表达增强的肝细胞周围有活化的星状细胞，产生转化生长因子-β。因此，癌前病变已经逃脱了转化生长因子-β的调控。(3)NK细胞可能攻击未成熟的再生肝细胞，延缓肝再生。

The reguration of hepatocyte regeneration has been thought the balane betwen inhibitory cytokines i. e. TGF-β and accelerating cytokines i. e. HGF.It has been reported that main TGF-b producing cell is the stellate cell which palys an important role of fibrosis in the liver. Under chronic inflamatory condition, either regenerated hepatocyte or extarcellular matrix, which stellate cell mainly produces, will replace the necrotic tissue. Also NK cell may be involved in the regulation of hepatocyte regeneration. The results of this study are followings ;(1) Pig serum treatment twice a week induced hepatic fibrosis with increased TGF-β expression and 70% hepatectomy of this TGF-β induced liver showed retarded regeneration compared with normal liver.(2) Choline deficient diet induced liver cirrhosis with preneoplastic lesions and hepatocellular carcinoma with incerased TGF-b expression by activated stellate cell and preneoplastic lesions are surrounded with activated stellate cell, producing TGF-β The extent of growth (regeneration) rate of these hepatocytes in the preneoplastic lesions is more than that of normal hepatocytes. Thus preneoplastic lesions are already escaped from the regulation of TGF-β.(3) NK cell may attack inmature regenerated hepatocytes and retard hepatic regeneration.