ANGIOTENSIN-II INDUCES CELLULAR HYPERTROPHY IN CULTURED MURINE PROXIMAL TUBULAR CELLS
ANGIOTENSIN-II INDUCES CELLULAR HYPERTROPHY IN CULTURED MURINE PROXIMAL TUBULAR CELLS
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DOI：
10.1152/ajprenal.1990.259.5.f768
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发表时间：
1990-11-01
影响因子：
--
通讯作者：
NEILSON, EG
中科院分区：
文献类型：
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作者：
WOLF, G;NEILSON, EG
在本研究中，我们证明了在培养物中表达血管紧张素II（ANG II）受体[解离常数（K（d））= 0.89 nM;受体密度（R（o））= 46，900个受体/细胞]的小鼠近端肾小管细胞系（MCT细胞）在每天加入外源性ANG II（10（-8）M）后可诱导肥大。这种肥大反应的特点是总细胞蛋白含量的增加，由[H-3]亮氨酸掺入到可沉淀的蛋白质的增强，并通过细胞荧光染色的细胞大小的增加。在不存在细胞增殖的情况下，这种导致MCT细胞增大的ANG II效应是可以证明的。然而，MCT细胞的增殖可以由表皮生长因子（EGF）或血小板衍生生长因子（PDGF）诱导，并且用ANG II预处理静止的MCT细胞进一步增强EGF诱导的细胞分裂。ANG II诱导的MCT细胞肥大是因子特异性的，因为它可以被saralasin阻断，而不是由血管紧张素I（ANG I）诱导的。这种肥大反应也是独立的前列腺素E2的合成，但可转导百日咳毒素敏感的G蛋白和参与，在一定程度上，激活Na+-H+交换。此外，ANG Ⅱ、EGF和/或PDGF可诱导细胞癌基因c-fos、c-myc、c-N-ras，但不诱导c-cis，这表明早期基因激活可能不是肥大的特异性先决条件。我们的研究结果表明，血管紧张素II，在文化中，可以是一个单一的因素事件能够诱导近端肾小管细胞肥大。
In the present study we demonstrate that a murine proximal tubular cell line (MCT cells), expressing angiotensin II (ANG II) receptors [dissociation constant (K(d)) = 0.89 nM; receptor density (R(o)) = 46,900 receptors/cell] in culture, can be induced to hypertrophy after the daily addition of exogenous ANG II (10(-8) M). This hypertrophic response was characterized by an increase in total cellular protein content, by an enhancement of [H-3]leucine incorporation into precipitable proteins, and by an augmentation in cell size by cytofluorography. This ANG II effect producing MCT cell enlargement was demonstrable in the absence of cellular proliferation. Proliferation of MCT cells, however, could be induced by epidermal growth factor (EGF) or platelet-derived growth factor (PDGF), and pretreatment of rested MCT cells with ANG II further enhanced EGF-induced cell division. ANG II-induced hypertrophy in MCT cells was factor specific, in that it could be blocked with saralasin, and not induced by angiotensin I (ANG I). This hypertrophic response was also independent of prostaglandin E2 synthesis but was transducable by pertussis toxin-sensitive G proteins and involved, to some extent, the activation of Na+-H+ exchange. ANG II, as well as EGF and/or PDGF, moreover, could induce the cellular oncogenes c-fos, c-myc, c-N-ras, but not c-cis, which suggests that early gene activation is probably not a specific prerequisite for hypertrophy. Our findings demonstrate that ANG II, in culture, can be a single-factor event capable of inducing hypertrophy in proximal tubular cells.