Jeon Un Sil, Han Ki-Hwan, Park Soo-Hyun, Lee Sang Do, Sheen Mee Rie, Jung Ju-Young, Kim Wan Young, Sands Jeff M, Kim Jin, Kwon H Moo
Dept. of Medicine, University of Maryland, Baltimore, MD 21201, USA.
Am J Physiol Renal Physiol. 2007 Jul;293(1):F408-15. doi: 10.1152/ajprenal.00502.2006. Epub 2007 Apr 4.
Hypokalemia causes a significant decrease in the tonicity of the renal medullary interstitium in association with reduced expression of sodium transporters in the distal tubule. We asked whether hypokalemia caused downregulation of the tonicity-responsive enhancer binding protein (TonEBP) transcriptional activator in the renal medulla due to the reduced tonicity. We found that the abundance of TonEBP decreased significantly in the outer and inner medullas of hypokalemic rats. Underlying mechanisms appeared different in the two regions because the abundance of TonEBP mRNA was lower in the outer medulla but unchanged in the inner medulla. Immunohistochemical examination of TonEBP revealed cell type-specific differences. TonEBP expression decreased dramatically in the outer and inner medullary collecting ducts, thick ascending limbs, and interstitial cells. In the descending and ascending thin limbs, TonEBP abundance decreased modestly. In the outer medulla, TonEBP shifted to the cytoplasm in the descending thin limbs. As expected, transcription of aldose reductase, a target of TonEBP, was decreased since the abundance of mRNA and protein was reduced. Downregulation of TonEBP appeared to have also contributed to reduced expression of aquaporin-2 and UT-A urea transporters in the renal medulla. In cultured cells, expression and activity of TonEBP were not affected by reduced potassium concentrations in the medium. These data support the view that medullary tonicity regulates expression and nuclear distribution of TonEBP in the renal medulla in cell type-specific manners.
低钾血症会导致肾髓质间质张力显著降低，同时远端小管中钠转运体的表达减少。我们研究了低钾血症是否由于张力降低导致肾髓质中张力反应增强子结合蛋白（TonEBP）转录激活因子的下调。我们发现，低钾血症大鼠的外髓质和内髓质中TonEBP的丰度显著降低。两个区域的潜在机制似乎有所不同，因为外髓质中TonEBP mRNA的丰度较低，而内髓质中则没有变化。对TonEBP的免疫组织化学检查揭示了细胞类型特异性差异。TonEBP在外髓质和内髓质集合管、厚升支和间质细胞中的表达显著降低。在降支细段和升支细段中，TonEBP的丰度略有降低。在外髓质中，TonEBP在降支细段转移到细胞质中。正如预期的那样，由于mRNA和蛋白质的丰度降低，TonEBP的靶标醛糖还原酶的转录减少。TonEBP的下调似乎也导致了肾髓质中水通道蛋白-2和UT-A尿素转运体表达的降低。在培养细胞中，培养基中钾浓度降低不会影响TonEBP的表达和活性。这些数据支持这样一种观点，即髓质张力以细胞类型特异性方式调节肾髓质中TonEBP的表达和核分布。
