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首页> 外文期刊>RSC Advances >Pharmacological inhibition of fatty acid-binding protein 4 (FABP4) protects against renal ischemia-reperfusion injury
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Pharmacological inhibition of fatty acid-binding protein 4 (FABP4) protects against renal ischemia-reperfusion injury

机译：脂肪酸结合蛋白4（FABP4）的药理抑制保护肾缺血再灌注损伤

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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）是内质网（ER）应激和细胞凋亡在糖尿病和动脉粥样硬化的关键介质。研究还证实，循环FABP4取决于在慢性肾脏病（CKD）肾功能急性肾损伤（AKI）的患者。然而，FABP4在AKI的功能仍然知之甚少。本研究的目的是调查FABP4的缺血再灌注损伤的作用（I / R）诱导的AKI。在本研究中，肾I / R损伤触发相比深水的FABP4基因和蛋白在细胞核和小鼠肾组织的肾小管细胞的细胞质的高表达。预处理BMS309403，FABP4的剂量20毫克公斤（-1）d（-1）4 d的高度选择性抑制剂，显著减少的血清肌酸酐水平，以改善急性肾功能不全和减毒肾小管在受伤肾脏的损伤。 FABP4的药理学抑制也降低末端转移酶介导的dUTP缺口末端标记（TUNEL）阳性凋亡的肾小管细胞的数目，并伴有切割胱天蛋白酶-3表达的下调。此外，FABP4抑制剂的口服给药导致ER应激的显著衰减在I / R表示由它的制造者蛋白葡萄糖调节蛋白78（GRP78），C / EBP同源蛋白质（CHOP），和caspase-12的表达受伤肾脏。在体外，FABP4在人肾近端小管细胞系（HK-2细胞）的表达增加诱导缺氧，随后复氧（HR）和FABP4抑制剂导致细胞凋亡和ER应激在一个HR-衰减显著诱导HK-2细胞。总之，这些研究结果表明，FABP4促成了我的发病机制/ R诱导的AKI，并建议FABP4的抑制可能是治疗AKI有希望的治疗策略。

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  • 来源
    《RSC Advances》 |2018年第27期|共8页
  • 作者

    Shi Min; Huang Rongshuang; Guo Fan; Li Lingzhi; Feng Yanhuan; Wei Zhengjie; Zhou Li; Ma Liang; Fu Ping;

  • 作者单位

    Sichuan Univ West China Hosp Div Nephrol Kidney Res Inst 37 Guoxue Allay Chengdu 610041 Peoples R China;

    Sichuan Univ West China Hosp Div Nephrol Kidney Res Inst 37 Guoxue Allay Chengdu 610041 Peoples R China;

    Sichuan Univ West China Hosp Div Nephrol Kidney Res Inst 37 Guoxue Allay Chengdu 610041 Peoples R China;

    Sichuan Univ West China Hosp Div Nephrol Kidney Res Inst 37 Guoxue Allay Chengdu 610041 Peoples R China;

    Sichuan Univ West China Hosp Div Nephrol Kidney Res Inst 37 Guoxue Allay Chengdu 610041 Peoples R China;

    Chengdu 7 High Sch Chengdu 610041 Peoples R China;

    Sichuan Univ West China Hosp Div Nephrol Kidney Res Inst 37 Guoxue Allay Chengdu 610041 Peoples R China;

    Sichuan Univ West China Hosp Div Nephrol Kidney Res Inst 37 Guoxue Allay Chengdu 610041 Peoples R China;

    Sichuan Univ West China Hosp Div Nephrol Kidney Res Inst 37 Guoxue Allay Chengdu 610041 Peoples R China;

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  • 中图分类 化学;
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