Regulation of rat proximal tubule epithelial cell growth by fibroblast growth factors, insulin-like growth factor-1 and transforming growth factor-beta, and analysis of fibroblast growth factors in rat kidney.
Regulation of rat proximal tubule epithelial cell growth by fibroblast growth factors, insulin-like growth factor-1 and transforming growth factor-beta, and analysis of fibroblast growth factors in rat kidney.
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成纤维细胞生长因子、胰岛素样生长因子-1和转化生长因子-β对大鼠近曲小管上皮细胞生长的调节以及大鼠肾脏成纤维细胞生长因子的分析。
DOI：
10.1002/jcp.1041480216
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发表时间：
1991
影响因子：
5.6
通讯作者：
Stevens,JL
中科院分区：
文献类型：
--
作者：
Zhang,GH;Ichimura,T;Wallin,A;Kan,M;Stevens,JL
生长因子可能在调节近曲小管上皮细胞的生长中起重要作用。为了确定哪些生长因子可能参与，我们研究了在限定培养基中培养的大鼠肾近端小管上皮（RPTE）细胞中各种纯化因子的促有丝分裂性。成纤维细胞生长因子aFGF（酸性FGF）和bFGF（碱性FGF）以剂量依赖性方式刺激DNA合成，ED 50值分别为4.5和3.2 ng/ml;它们的作用不是累加的。在有霍乱毒素的培养基中，aFGF和bFGF都能代替胰岛素或表皮生长因子（EGF）达到细胞生长的最高水平，但不能代替霍乱毒素。霍乱毒素特异性地增强FGF对DNA合成的作用。在高细胞密度下，胰岛素和胰岛素样生长因子1（IGF-1）比EGF，FGF和霍乱毒素更有效地诱导DNA合成。细胞生长所需的高浓度（0.2 - 1.0 μg/ml）胰岛素可以被低浓度的IGF-1（10 - 20 ng/ml）替代，表明胰岛素可能通过与IGF-1受体的低亲和力相互作用发挥作用。转化生长因子-β1（TGF-β1）以浓度依赖性方式抑制单个因子和因子组合诱导的DNA合成。北方印迹分析显示，大鼠肾脏中存在TGF-β1、IGF-1和aFGF的mRNA，但不存在bFGF。蛋白质印迹分析和生物测定数据证实，大鼠肾脏中的大部分FGF样蛋白是aFGF。这些数据表明，除了EGF、IGFs和TGF-β外，FGF也可能是体内和体外近端小管上皮细胞生长的重要肾源性调节因子。
Growth factors may play an important role in regulating the growth of the proximal tubule epithelium. To determine which growth factors could be involved, we have investigated the mitogenicity of various purified factors in rat kidney proximal tubule epithelial (RPTE) cells cultured in defined medium. Fibroblast growth factors, aFGF (acidic FGF) and bFGF (basic FGF), stimulate DNA synthesis in a dose‐dependent manner, with ED50 values of 4.5 and 3.2 ng/ml, respectively; their effects are not additive. With cholera toxin in the medium, both aFGF and bFGF can replace insulin or epidermal growth factor (EGF) to attain the maximum level of cell growth, but they cannot eplace cholera toxin. Cholera toxin specifically potentiates the effects of FGFs on DNA synthesis. At high cell density, both insulin and insulin‐like growth factor 1 (IGF‐1) induce DNA synthesis more effectively than EGF, FGFs and cholera toxin. The high concentration (0.2‐1.0 μg/ml) of insulin required for cell growth can be replaced by a low concentration of IGF‐1 (10‐20 ng/ml), indicating that insulin probably acts through a low affinity interaction with the IGF‐1 receptor. Transforming growth factor‐β1 (TGF‐β1) inhibits DNA synthesis induced by individual factors and combinations of factors in a concentration‐dependent manner. Northern blot analysis shows that mRNA for TGF‐β1, IGF‐1, and aFGF, but not bFGF are present in rat kidney. Western blot analysis and bioassay data confirmed that the majority of FGF‐like protein in rat kidney is aFGF. The data suggest that in addition to EGF, IGFs, and TGF‐β, FGFs may also be important kidney‐derived regulators of proximal tubule epithelial cell growth in vivo and in vitro.