• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>RSC Advances >Pharmacological inhibition of fatty acid-binding protein 4 (FABP4) protects against renal ischemia-reperfusion injury
【24h】

Pharmacological inhibition of fatty acid-binding protein 4 (FABP4) protects against renal ischemia-reperfusion injury

机译：抑制脂肪酸结合蛋白4（FABP4）的药理作用可防止肾脏缺血再灌注损伤

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

摘要

Fatty acid-binding protein 4 (FABP4) is a key mediator of endoplasmic reticulum (ER) stress and apoptosis in diabetes and atherosclerosis. Studies also confirmed that circulating FABP4 depended on renal function in chronic kidney disease (CKD) and acute kidney injury (AKI) patients. However, the function of FABP4 in AKI remains poorly understood and the aim of this study was to investigate the role of FABP4 in ischemia-reperfusion (I/R)-induced AKI. In the present study, renal I/R injury triggered the high expression of the FABP4 gene and protein in the nucleus and cytoplasm of tubular cells of mouse kidney tissue compared to that of Sham. Pretreatment with BMS309403, a highly selective inhibitor of FABP4 at a dose of 20 mg kg ~(?1) d ~(?1) for 4 d, significantly reduced serum creatinine levels to improve acute renal dysfunction and attenuated renal tubular damage in injured kidneys. Pharmacological inhibition of FABP4 also decreased the number of TdT-mediated dUTP nick-end labeling (TUNEL) positive apoptotic tubular cells, accompanied by the down-regulation of cleaved-caspase-3 expression. Furthermore, oral administration of FABP4 inhibitor resulted in a significant attenuation of ER stress indicated by its maker proteins expression of glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), and caspase-12 in I/R injured kidneys. In vitro , the increased expression of FABP4 in the human renal proximal tubule cell line (HK-2 cell) was induced by hypoxia followed by reoxygenation (HR) and the FABP4 inhibitor resulted in a significant attenuation of cell apoptosis and ER stress in HR-induced HK-2 cells. In summary, these findings indicated that FABP4 contributed to the pathogenesis of I/R-induced AKI and suggested that the inhibition of FABP4 might be a promising therapeutic strategy for AKI treatment.
机译：脂肪酸结合蛋白4（FABP4）是糖尿病和动脉粥样硬化中内质网（ER）应激和细胞凋亡的关键介质。研究还证实，循环中的FABP4依赖于慢性肾脏疾病（CKD）和急性肾损伤（AKI）患者的肾功能。然而，FABP4在AKI中的功能仍然知之甚少，本研究的目的是研究FABP4在缺血再灌注（I / R）诱导的AKI中的作用。在本研究中，与假手术相比，肾脏I / R损伤触发了小鼠肾脏组织小管细胞核和细胞质中FABP4基因和蛋白质的高表达。用BMS309403（一种高度选择性的FABP4抑制剂）以20 mg kg〜（？1）d〜（？1）的剂量预处理4 d，可显着降低血清肌酐水平，以改善急性肾功能不全并减轻受损肾脏的肾小管损伤。 FABP4的药理抑制作用还减少了TdT介导的dUTP缺口末端标记（TUNEL）阳性凋亡小管细胞的数量，并伴随着Caspase-3裂解表达的下调。此外，口服FABP4抑制剂可显着减轻ER应激，这是由I / R受损肾脏中的葡萄糖调节蛋白78（GRP78），C / EBP同源蛋白（CHOP）和caspase-12的启动子蛋白表达所指示的。 。在体外，缺氧然后再充氧（HR）诱导人肾近端肾小管细胞系（HK-2细胞）中FABP4表达的增加，FABP4抑制剂导致HR-细胞凋亡和ER应激显着减弱。诱导的HK-2细胞。总之，这些发现表明FABP4促成了I / R诱导的AKI的发病机理，并表明抑制FABP4可能是AKI治疗的一种有前途的治疗策略。

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