Changes in TGF‐β receptors of rat hepatocytes during primary culture and liver regeneration: Increased expression of TGF‐β receptors associated with increased sensitivity to TGF‐β‐mediated growth inhibition
Changes in TGF‐β receptors of rat hepatocytes during primary culture and liver regeneration: Increased expression of TGF‐β receptors associated with increased sensitivity to TGF‐β‐mediated growth inhibition
复制标题
DOI：
10.1002/(sici)1097-4652(199809)176:3
复制
发表时间：
1998-09
影响因子：
5.6
通讯作者：
Y. Nishikawa;Meifang Wang;B. Carr
中科院分区：
文献类型：
--
作者：
Y. Nishikawa;Meifang Wang;B. Carr
为了阐明转化生长因子-β（TGF-β）及其受体在肝细胞生长中的作用，我们研究了大鼠静息和再生肝细胞中TGF-β1及其受体的表达以及对TGF-β1蛋白生长抑制的敏感性。在来源于静息肝脏的肝细胞中，TGF-β II型受体（Tβ R-II）、胰岛素样生长因子-II/甘露糖6-磷酸受体（IGF-II/M-6-PR）和TGF-β1的mRNA在原代培养中随时间增加。使用125 I-TGF-β1通过受体亲和标记试验检测的细胞表面TGF-β受体蛋白（Tβ R-I、II和III）也增加，尤其是在培养48小时后。肝细胞对DNA合成的抑制更敏感，当TGF-β1蛋白在培养后期加入时，对应于TGF-β受体的增加。在部分肝切除术（PH）后再生肝的肝细胞中，与静息肝的肝细胞相比，发现Tβ R-I、Tβ R-II、Tβ R-III、IGF-II/M-6-PR和TGF-β1 mRNA增加。同样，使用TGF-β受体亲和标记试验，发现PH肝脏的肝细胞与静息肝脏的肝细胞相比，Tβ R-I、II和III蛋白增加，峰值出现在PH后4天。当细胞附着于肝细胞培养物后短时间（6或24小时）加入TGF-β1蛋白时，与静息肝脏相比，其在再生肝细胞中更有效地抑制DNA合成。我们的研究结果表明，肝细胞TGF-β受体和对TGF-β1蛋白生长抑制的敏感性一起变化，并在肝再生过程中以及原代培养条件下受到调节。J.细胞。176：612-623，1998。© 1998 Wiley利斯公司
To clarify the role of transforming growth factor‐β (TGF‐β) and its receptors in hepatocyte growth, we studied the expression of TGF‐β1 and its receptors and the sensitivity to growth inhibition by TGF‐β1 protein in rat hepatocytes derived from resting and regenerating livers. In hepatocytes derived from resting livers, mRNAs for TGF‐β type II receptor (TβR‐II), insulin‐like growth factor‐II/mannose 6‐phosphate receptor (IGF‐II/M‐6‐PR), and TGF‐β1 increased with time in primary culture. The cell surface TGF‐β receptor proteins (TβR‐I, II, and III), examined by the receptor affinity‐labeling assay using 125I‐TGF‐β1, also increased, especially after 48 hr of culture. Hepatocytes were more sensitive to inhibition of DNA synthesis, when the TGF‐β1 protein was added at later times in culture, corresponding to the presence of increased TGF‐β receptors. In hepatocytes from regenerating livers after a partial hepatectomy (PH), an increase of TβR‐I, TβR‐II, TβR‐III, IGF‐II/M‐6‐PR, and TGF‐β1 mRNAs was found, compared with hepatocytes from resting livers. Similarly, using TGF‐β receptor affinity‐labeling assay, hepatocytes from PH livers were found to have an increase in TβR‐I, II, and III proteins, with a peak at 4 days post‐PH, compared with hepatocytes from resting livers. When TGF‐β1 protein was added for a short period (6 or 24 hr) after cell attachment to hepatocyte cultures, it inhibited DNA synthesis more effectively in hepatocytes from regenerating compared with resting livers. Our results show that hepatocyte TGF‐β receptors and sensitivity to growth inhibition by TGF‐β1 protein change together and are modulated during liver regeneration, as well as during the conditions of primary culture. J. Cell. Physiol. 176:612–623, 1998. © 1998 Wiley‐Liss, Inc.