• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cellular Physiology and Biochemistry >Increased Fatty Acid Oxidation in Differentiated Proximal Tubular Cells Surviving a Reversible Episode of Acute Kidney Injury
【24h】

Increased Fatty Acid Oxidation in Differentiated Proximal Tubular Cells Surviving a Reversible Episode of Acute Kidney Injury

机译：在急性肾损伤的可逆发作中存活的分化型近端小管细胞中的脂肪酸氧化增加

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Background/Aims Fatty acid oxidation (FAO), the main source of energy produced by tubular epithelial cells in the kidney, was found to be defective in tubulo-interstitial samples dissected out in kidney biopsies from patients with chronic kidney disease (CKD). Experimental data indicated that this decrease was a strong determinant of renal fibrogenesis, hence a focus for therapeutic interventions. Nevertheless, whether persistently differentiated renal tubules, surviving in a pro-fibrotic environment, also suffer from a decrease in FAO, is currently unknown. Methods To address this question, we isolated proximal tubules captured ex vivo on the basis of the expression of an intact brush border antigen (Prominin-1) in C57BL6/J mice subjected to a controlled, two-hit model of renal fibrosis (reversible ischemic acute kidney injury (AKI) or sham surgery, followed by angiotensin 2 administration). A transcriptomic high throughput sequencing was performed on total mRNA from these cells, and on whole kidneys. Results In contrast to mice subjected to sham surgery, mice with a history of AKI displayed histologically more renal fibrosis when exposed to angiotensin 2. High throughput RNA sequencing, principal component analysis and clustering showed marked consistency within experimental groups. As expected, FAO transcripts were decreased in whole fibrotic kidneys. Surprisingly, however, up- rather than down-regulation of metabolic pathways (oxidative phosphorylation, fatty acid metabolism, glycolysis, and PPAR signalling pathway) was a hallmark of the differentiated tubules captured from fibrotic kidneys. Immunofluorescence co-staining analysis confirmed that the expression of FAO enzymes was dependent of tubular trophicity. Conclusions These data suggest that in differentiated proximal tubules energetic hyperactivity is promoted concurrently with organ fibrogenesis.
机译：背景/目的脂肪酸氧化（FAO）是肾脏中肾小管上皮细胞产生的主要能量来源，被发现在从慢性肾脏病（CKD）患者的肾脏活检中解剖出的肾小管间质样品中存在缺陷。实验数据表明，这种下降是肾脏纤维发生的重要决定因素，因此是治疗干预的重点。然而，目前尚不知道在促纤维化环境中存活的持续分化的肾小管是否也遭受粮农组织的减少。方法为了解决这个问题，我们基于完整的刷状边界抗原（Prominin-1）在受控制的两次打击的肾纤维化模型（可逆性缺血）的C57BL6 / J小鼠中分离了离体捕获的近端肾小管急性肾损伤（AKI）或假手术，然后给予血管紧张素2）。对来自这些细胞以及整个肾脏的总mRNA进行转录组高通量测序。结果与接受假手术的小鼠相比，具有AKI历史的小鼠在暴露于血管紧张素2时在组织学上表现出更多的肾脏纤维化。高通量RNA测序，主成分分析和聚类分析显示实验组内具有显着一致性。如预期的那样，在整个纤维化肾脏中，粮农组织的转录本有所减少。然而，令人惊讶的是，代谢途径（氧化磷酸化，脂肪酸代谢，糖酵解和PPAR信号传导途径）的上调而非下调是从纤维化肾脏捕获的分化小管的标志。免疫荧光共染色分析证实，FAO酶的表达依赖于小管营养。结论这些数据表明，在分化的近端小管中，能量亢进与器官纤维发生同时被促进。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号