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首页> 外文期刊>American Journal of Physiology >Aldosterone and tight junctions: modulation of claudin-4 phosphorylation in renal collecting duct cells.
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Aldosterone and tight junctions: modulation of claudin-4 phosphorylation in renal collecting duct cells.

机译：醛固酮和紧密连接：肾脏收集管细胞中claudin-4磷酸化的调节。

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Aldosterone classically modulates Na transport in tight epithelia such as the renal collecting duct (CD) through the transcellular route, but it is not known whether the hormone could also affect paracellular permeability. Such permeability is controlled by tight junctions (TJ) that form a size- and charge-selective barrier. Among TJ proteins, claudin-4 has been highlighted as a key element to control paracellular charge selectivity. In RCCD2 CD cells grown on filters, we have identified novel early aldosterone effects on TJ. Endogenous claudin-4 abundance and cellular localization were unaltered by aldosterone. However, the hormone promoted rapid (within 15-20 min) and transient phosphorylation of endogenous claudin-4 on threonine residues, without affecting tyrosine or serine; this event was fully developed at 10 nM aldosterone and appeared specific for aldosterone (because it is not observed after dexamethasone treatment and it depends on mineralocorticoid receptor occupancy). Within the same delay,aldosterone also promoted an increased apical-to-basal passage of 125I (a substitute for 36Cl), whereas 22Na passage was unaffected; paracellular permeability to [3H]mannitol was also reduced. Later on (45 min), a fall in transepithelial resistance was observed. These data indicate that aldosterone modulates TJ properties in renal epithelial cells.
机译：醛固酮经典地调节了钠在紧致上皮细胞（如肾收集管（CD））中通过跨细胞途径的转运，但尚不清楚激素是否还会影响细胞旁通透性。这种渗透性由形成尺寸和电荷选择性势垒的紧密结（TJ）控制。在TJ蛋白中，claudin-4已被突出显示为控制细胞旁电荷选择性的关键元素。在滤器上生长的RCCD2 CD细胞中，我们发现了对TJ的新型早期醛固酮作用。醛固酮不会改变内源性claudin-4的丰度和细胞定位。然而，该激素可促进苏氨酸残基上内源性claudin-4的快速（15-20分钟内）和瞬时磷酸化，而不会影响酪氨酸或丝氨酸。此事件在10 nM醛固酮时已完全发展，并且似乎对醛固酮具有特异性（因为在地塞米松治疗后未观察到，这取决于盐皮质激素受体的占用）。在相同的延迟时间内，醛固酮还促进了125I（替代36Cl）的根尖至基底的通道增加，而22Na的通道不受影响。对[3H]甘露醇的细胞旁通透性也降低。随后（45分钟），观察到跨上皮阻力下降。这些数据表明醛固酮调节肾上皮细胞中的TJ特性。

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