BSC-1 growth inhibitor transforms a mitogenic stimulus into a hypertrophic stimulus for renal proximal tubular cells: relationship to Na+/H+ antiport activity.
BSC-1 growth inhibitor transforms a mitogenic stimulus into a hypertrophic stimulus for renal proximal tubular cells: relationship to Na+/H+ antiport activity.
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BSC-1 生长抑制剂将有丝分裂刺激转化为肾近端肾小管细胞肥大刺激：与 Na /H 逆向转运活性的关系。
DOI：
10.1073/pnas.82.18.6163
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发表时间：
1985
影响因子：
11.1
通讯作者：
Badie-Dezfooly,B
中科院分区：
文献类型：
--
作者：
Fine,LG;Holley,RW;Nasri,H;Badie-Dezfooly,B
肾肥大的特征是细胞大小和蛋白质含量增加，伴有轻微增生。这种细胞生长模式的控制机制尚未确定。目前的研究检查是否生长抑制剂阐述BSC-1肾上皮细胞（GI），它具有几乎相同的生物学特性，转化生长因子β（TGF-β），可以转化成肥大刺激原代培养的兔肾近端小管细胞的有丝分裂刺激。胰岛素（10 μ g/ml）加氢化可的松（50 nM）在24和48小时增加了这些细胞中每个细胞的蛋白质量、细胞体积和[3 H]胸苷掺入。GI/TGF-β（10单位/ml）对[3 H]胸苷掺入的刺激最小。当与胰岛素加氢化可的松一起加入时，GI/TGF-β抑制这些促有丝分裂剂对[3 H]胸苷掺入的刺激作用，但不阻止每个细胞蛋白质和细胞体积的增加-即，细胞发生肥大。这种模式持续48小时的事实表明，GI/TGF-β对有丝分裂刺激的DNA合成产生了长期的抑制作用，而不是延迟其发作。阿米洛利敏感的Na+摄取（Na+/H+反向转运活性的指示）与每个细胞的蛋白质和细胞体积相关，而不是与DNA合成相关。从近端肾小管细胞收获的条件培养基的P60凝胶色谱分离产生抑制BSC-1细胞和CCL 64细胞中[3 H]胸苷掺入的组分;对这些细胞系的相对抑制活性和色谱行为与GI/TGF-β观察到的相似。这些研究表明，细胞大小的控制可能受到自分泌机制的调节，该机制由改变对有丝分裂原的生长反应模式的生长抑制因子介导。
Renal hypertrophy is characterized by an increase in cell size and protein content with minimal hyperplasia. The mechanisms of control of this pattern of cell growth have not been determined. The present studies examined whether the growth inhibitor elaborated by BSC-1 kidney epithelial cells (GI), which has nearly identical biological properties to transforming growth factor beta (TGF-beta), could transform a mitogenic stimulus into a hypertrophic stimulus for rabbit renal proximal tubular cells in primary culture. Insulin (10 micrograms/ml) plus hydrocortisone (50 nM) increased the amount of protein per cell, cell volume, and [3H]thymidine incorporation at 24 and 48 hr in these cells. GI/TGF-beta (10 units/ml) led to a minimal stimulation of [3H]thymidine incorporation. When added together with insulin plus hydrocortisone, GI/TGF-beta inhibited the stimulatory effect of these mitogens on [3H]thymidine incorporation but did not block the increase in protein per cell and cell volume--i.e., the cells underwent hypertrophy. The fact that this pattern persisted for 48 hr indicated that GI/TGF-beta exerted a prolonged inhibitory effect on mitogenic-stimulated DNA synthesis rather than delaying its onset. Amiloride-sensitive Na+ uptake (indicative of Na+/H+ antiport activity) correlated with protein per cell and cell volume rather than with DNA synthesis. P60 gel chromatographic fractionation of conditioned medium harvested from proximal tubular cells yielded a fraction that inhibited [3H]thymidine incorporation in BSC-1 cells and CCL 64 cells; the relative inhibitory activity on these cell lines and the chromatographic behavior were similar to those observed with GI/TGF-beta. These studies indicate that the control of cell size may be regulated by autocrine mechanisms mediated by the elaboration of growth inhibitory factors that alter the pattern of the growth response to mitogens.