Burger-Kentischer A, Müller E, März J, Fraek M L, Thurau K, Beck F X
Department of Physiology, University of Munich, Germany.
Kidney Int. 1999 Apr;55(4):1417-25. doi: 10.1046/j.1523-1755.1999.00382.x.
Medullary cells of the concentrating kidney are exposed to high extracellular solute concentrations. It is well established that epithelial cells in this kidney region adapt osmotically to hypertonic stress by accumulating organic osmolytes. Little is known, however, of the adaptive mechanisms of a further medullary cell type, the papillary interstitial cell [renal papillary fibroblast (RPF)]. We therefore compared the responses of primary cultures of RPFs and papillary collecting duct (PCD) cells exposed to hypertonic medium.
In RPFs and PCD cells, organic osmolytes were determined by high-performance liquid chromatography; mRNA expression for organic osmolyte transporters [Na+/Cl(-)-dependent betaine transporter (BGT), Na(+)-dependent myo-inositol transporter (SMIT)], and the sorbitol synthetic and degrading enzymes [aldose reductase (AR) and sorbitol dehydrogenase (SDH), respectively] was determined by Northern blot analysis.
Exposure to hypertonic medium (600 mOsm/kg by NaCl addition) caused intracellular contents of glycerophosphorylcholine, betaine, myo-inositol, and sorbitol, but not free amino acids, to increase significantly in both RPFs and PCD cells. The rise in intracellular contents of these organic osmolytes was accompanied by enhanced expression of mRNAs coding for BGT, SMIT, and AR in both RPFs and PCD cells. SDH mRNA abundance, however, was unchanged. Nonradioactive in situ hybridization studies on sections from formalin-fixed and paraffin-embedded, normally concentrating kidneys showed strong expression of BGT, SMIT, and AR mRNAs in interstitial and collecting duct cells of the papilla, whereas expression of SDH mRNA was much weaker in both cell types.
These results suggest that both RPFs and PCD cells use similar strategies to adapt osmotically to the high interstitial NaCl concentrations characteristic for the inner medulla and papilla of the concentrating kidney.
浓缩尿液的肾脏髓质细胞暴露于高细胞外溶质浓度环境中。众所周知，该肾脏区域的上皮细胞通过积累有机渗透溶质来进行渗透适应高渗应激。然而，对于另一种髓质细胞类型，即肾乳头间质细胞[肾乳头成纤维细胞（RPF）]的适应机制却知之甚少。因此，我们比较了暴露于高渗培养基中的RPF原代培养物和肾乳头集合管（PCD）细胞的反应。
在RPF和PCD细胞中，通过高效液相色谱法测定有机渗透溶质；通过Northern印迹分析测定有机渗透溶质转运体[Na+/Cl(-)依赖性甜菜碱转运体（BGT）、Na(+)依赖性肌醇转运体（SMIT）]以及山梨醇合成和降解酶[分别为醛糖还原酶（AR）和山梨醇脱氢酶（SDH）]的mRNA表达。
暴露于高渗培养基（通过添加NaCl至600 mOsm/kg）导致RPF和PCD细胞中甘油磷酸胆碱、甜菜碱、肌醇和山梨醇的细胞内含量显著增加，但游离氨基酸含量未增加。这些有机渗透溶质细胞内含量的增加伴随着RPF和PCD细胞中编码BGT、SMIT和AR的mRNA表达增强。然而，SDH mRNA丰度未改变。对福尔马林固定、石蜡包埋的正常浓缩尿液的肾脏切片进行非放射性原位杂交研究显示，乳头间质和集合管细胞中BGT、SMIT和AR mRNA表达强烈，而两种细胞类型中SDH mRNA表达均较弱。
这些结果表明，RPF和PCD细胞都采用类似策略来进行渗透适应，以应对浓缩尿液的肾脏内髓质和乳头所特有的高间质NaCl浓度。
