The thiazide-sensitive Na-Cl cotransporter is an aldosterone-induced protein
The thiazide-sensitive Na-Cl cotransporter is an aldosterone-induced protein
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DOI：
10.1073/pnas.95.24.14552
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发表时间：
1998-11-24
影响因子：
11.1
通讯作者：
Knepper, MA
中科院分区：
文献类型：
--
作者：
Kim, GH;Masilamani, S;Knepper, MA
虽然集合管被认为是盐皮质激素调节肾脏钠转运的主要部位，但最近的证据表明远曲小管可能是盐皮质激素作用的部位。为了研究盐皮质激素是否调节噻嗪敏感性钠-氯协同转运蛋白（TSC）的表达，TSC是远曲小管细胞的主要顶端钠进入途径，我们制备了一种亲和纯化的针对TSC的肽定向抗体。在免疫印迹上，该抗体识别来自肾皮质但不来自肾髓质的膜组分中的突出的165-kDa条带。免疫荧光免疫细胞化学显示TSC标记仅在远曲小管细胞中。半定量免疫印迹研究表明，低NaCl饮食大鼠肾皮质中TSC表达大幅增加（对照饮食的207 +/- 21%）。组织切片中的免疫荧光定位证实了TSC表达的强烈增加。用持续皮下输注醛固酮治疗大鼠10天也增加了TSC表达（对照的380 +/-58%）。此外，口服盐皮质激素氟氢可的松治疗大鼠7天，增加TSC表达（对照组的656 +/- 114%），我们得出结论，远曲小管是盐皮质激素醛固酮的重要作用部位，其强烈上调TSC的表达。
Although the collecting duct is regarded as the primary site at which mineralocorticoids regulate renal sodium transport in the kidney, recent evidence points to the distal convoluted tubule as a possible site of mineralocorticoid action. To investigate whether mineralocorticoids regulate the expression of the thiazide-sensitive Na-Cl cotransporter (TSC), the chief apical sodium entry pathway of distal convoluted tubule cells, we prepared an affinity-purified, peptide-directed antibody to TSC, On immunoblots, the antibody recognized a prominent 165-kDa band in membrane fractions from the renal cortex but not from the renal medulla. Immunofluorescence immunocytochemistry showed TSC labeling only in distal convoluted tubule cells, Semiquantitative immunoblotting studies demonstrated a large increase in TSC expression in the renal cortex of rats on a low-NaCl diet (207 +/- 21% of control diet). Immunofluorescence localization in tissue sections confirmed the strong increase in TSC expression, Treatment of rats for 10 days with a continuous subcutaneous infusion of aldosterone also increased TSC expression (380 +/- 58% of controls). Furthermore, 7-day treatment of rats with an orally administered mineralocorticoid, fludrocortisone, increased TSC expression (656 +/- 114% of controls), We conclude that the distal convoluted tubule is an important site of action of the mineralocorticoid aldosterone, which strongly up-regulates the expression of TSC.