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E-钙黏蛋白和紧密连接蛋白 4 在成年大鼠肾脏中的表达具有昼夜节律性。

E-cadherin and claudin-4 expression has circadian rhythm in adult rat kidney.

机构信息

Department of Geriatrics and Nephrology, Osaka University School of Medicine, Suita, Osaka, Japan.

出版信息

J Nephrol. 2010 Jan-Feb;23(1):102-10.

Abstract

BACKGROUND

Urinary sodium excretion varies during the day. It is unknown whether expression levels of cell-cell junctions in the kidney are dynamic and associated with urinary sodium excretion.

METHODS

Adult Sprague Dawley rats were fed ad libitum or exclusively during the day, or kept under fasting condition. We measured expression levels of Per2, E-cadherin and claudin-4 as representative molecules of the peripheral circadian clock, adherens junctions and tight junctions, respectively. We also measured sodium concentration in urine. Effects of aldosterone on expression levels of Per2 and claudin-4 were also studied. To see proliferating cells in the kidney, rats were labeled with 5-bromo-2'-deoxyuridine.

RESULTS

In rats fed ad libitum, Per2, E-cadherin and claudin-4 mRNA showed robust circadian oscillation: the correlation coefficients (R values) of the cosinor fitting curves with a 24-hour cycle were 0.928, 0.999 and 0.983, respectively. Oscillation phases of these molecules shifted in response to restricted feeding (R=0.922, R=0.815 and R=0.821, respectively). E-cadherin and claudin-4 proteins also oscillated circadianly under ad libitum feeding (R=0.851 and R=0.999, respectively), which shifted in response to the restricted feeding (R=0.811 and R=0.985, respectively). Urinary sodium excretion was low when protein levels of E-cadherin and claudin-4 were high. Aldosterone or cell division did not account for mRNA oscillation of claudin-4 or E-cadherin in the kidney.

CONCLUSIONS

Expression of E-cadherin and claudin-4 has a circadian rhythm. The dynamic change in protein levels of E-cadherin and claudin-4 seems to coincide with that in the level of sodium excretion.

摘要

背景

尿钠排泄量在一天中是变化的。细胞-细胞连接在肾脏中的表达水平是否具有动态变化特征,以及这种变化是否与尿钠排泄有关,目前尚不清楚。

方法

成年 Sprague Dawley 大鼠自由进食或仅在白天进食,或禁食。我们分别测量了外周生物钟代表性分子 Per2、黏附连接代表性分子 E-钙黏蛋白和紧密连接代表性分子 claudin-4 的表达水平。同时,我们还测量了尿液中的钠浓度。我们还研究了醛固酮对 Per2 和 claudin-4 表达水平的影响。为了观察肾脏中的增殖细胞,大鼠被 5-溴-2'-脱氧尿苷标记。

结果

在自由进食的大鼠中,Per2、E-钙黏蛋白和 claudin-4mRNA 表现出明显的昼夜节律性振荡:用 24 小时周期进行正余弦拟合曲线的相关系数(R 值)分别为 0.928、0.999 和 0.983。这些分子的振荡相位随限时进食而发生改变(R=0.922、R=0.815 和 R=0.821)。在自由进食条件下,E-钙黏蛋白和 claudin-4 蛋白也呈昼夜节律性振荡(R=0.851 和 R=0.999),这种振荡相位随限时进食而发生改变(R=0.811 和 R=0.985)。当 E-钙黏蛋白和 claudin-4 蛋白水平较高时,尿钠排泄量较低。醛固酮或细胞分裂并不能解释肾脏中 claudin-4 或 E-钙黏蛋白的 mRNA 振荡。

结论

E-钙黏蛋白和 claudin-4 的表达具有昼夜节律性。E-钙黏蛋白和 claudin-4 蛋白水平的动态变化似乎与钠排泄水平的变化一致。

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