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首页> 外文期刊>The Journal of Nutritional Biochemistry >MD2 blockade prevents oxLDL-induced renal epithelial cell injury and protects against high-fat-diet-induced kidney dysfunction
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MD2 blockade prevents oxLDL-induced renal epithelial cell injury and protects against high-fat-diet-induced kidney dysfunction

机译：MD2封锁可防止Oxldl诱导的肾上皮细胞损伤，并防止高脂饮食诱导的肾功能障碍

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摘要

There is a strong epidemiological link between obesity, a growing worldwide concern, and kidney disease. Emerging evidence indicates that the pathogenic basis of obesity-related kidney disease may be attributed to Toll-like receptor 4 (TLR4) of the innate immune system. We hypothesized that renal epithelial cell injury in response to oxidized low-density lipoprotein (oxLDL) requires myeloid differentiation factor 2 (MD2), a co-receptor of TLR4. Moreover, we also hypothesized that renal dysfunction is MD2-dependent in the high-fat diet (HFD) mouse model. Results indicated that the MD2 selective inhibitor (L6H21) abrogated the oxLDL-induced formation of MD2-TLR4 dimerization in the renal proximal tubular epithelial cell line NRK-52E. Further, MD2 blockade in NRK-52E cells using siRNA target sequences or L6H21 prevented oxLDL-induced cell injury as indicated by expression of profibrotic molecules, autophagic activity and apoptosis. Similarly, TLR4 knockdown in NRK-52E cells using siRNA target sequences prevented oxLDL-induced cell injury. In the HFD mouse model, MD2 knockout protected against development of kidney dysfunction and renal tissue injury, corroborating the observations observed in NRK-52E cells. Thus, the oxLDL-induced renal tubular epithelial cell profibrotic responses, autophagy and apoptosis were dependent on MD2, as were the renal dysfunction and tissue impairment in HFD mice. These are new findings indicating that the MD2-TLR4 immune signaling complex is a critical pathogenic factor in the development of kidney disease related to obesity or metabolic syndrome. (C) 2019 The Authors. Published by Elsevier Inc.
机译：肥胖之间存在强烈的流行病学联系，在全球范围内的关注和肾病之间。新兴的证据表明，肥胖相关肾病的致病基础可归因于天生免疫系统的Toll样受体4（TLR4）。我们假设肾上皮细胞损伤响应于氧化低密度脂蛋白（OXLDL）需要髓样分化因子2（MD2），TLR4的共同受体。此外，我们还假设肾功能障碍是MD2依赖于高脂饮食（HFD）小鼠模型。结果表明，MD2选择性抑制剂（L6H21）废除了雄性诱导的肾近侧管状上皮细胞系NRK-52E中的MD2-TLR4二聚化的形成。此外，使用SiRNA靶序列的NRK-52E细胞中的MD2阻断或L6H21预防oxldl诱导的细胞损伤，如通过表达型血频分子，自噬和凋亡。类似地，使用siRNA靶序列在NRK-52E细胞中敲低抗牛油诱导的细胞损伤。在HFD小鼠模型中，MD2敲除保护肾功能障碍和肾组织损伤的发育，证实了NRK-52E细胞中观察到的观察结果。因此，雄性肾小管上皮细胞的研究，自噬和凋亡依赖于MD2，同时肾功能不全和HFD小鼠中的组织损伤。这些是新发现，表明MD2-TLR4免疫信号传导复合物是与肥胖或代谢综合征有关的肾病发育的关键致病因子。 （c）2019年作者。 elsevier公司发布

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  • 作者

    Xu Sujing; Luo Wu; Xu Xiaohong; Qian Yuanyuan; Xu Zheng; Yu Weihui; Shan Xiaoou; Guan Xinfu; Lum Hazel; Zhou Huiping; Wang Yi;

  • 作者单位

    Wenzhou Med Univ Sch Pharmaceut Sci Chem Biol Res Ctr Wenzhou 325035 Zhejiang Peoples R China;

    Wenzhou Med Univ Sch Pharmaceut Sci Chem Biol Res Ctr Wenzhou 325035 Zhejiang Peoples R China;

    Wenzhou Med Univ Sch Pharmaceut Sci Chem Biol Res Ctr Wenzhou 325035 Zhejiang Peoples R China;

    Wenzhou Med Univ Sch Pharmaceut Sci Chem Biol Res Ctr Wenzhou 325035 Zhejiang Peoples R China;

    Wenzhou Med Univ Sch Pharmaceut Sci Chem Biol Res Ctr Wenzhou 325035 Zhejiang Peoples R China;

    Wenzhou Med Univ Affiliated Yueqing Hosp 1 Dept Endocrinol Wenzhou 325035 Zhejiang Peoples R China;

    Wenzhou Med Univ Affiliated Hosp 2 Wenzhou 325000 Zhejiang Peoples R China;

    Wenzhou Med Univ Affiliated Cangnan Hosp Wenzhou 325000 Zhejiang Peoples R China;

    Wenzhou Med Univ Sch Pharmaceut Sci Chem Biol Res Ctr Wenzhou 325035 Zhejiang Peoples R China;

    Wenzhou Med Univ Sch Pharmaceut Sci Chem Biol Res Ctr Wenzhou 325035 Zhejiang Peoples R China;

    Wenzhou Med Univ Sch Pharmaceut Sci Chem Biol Res Ctr Wenzhou 325035 Zhejiang Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 生物化学;
  • 关键词

    TLR4; MD2; oxLDL; Obesity; Kidney injury;

    机译：TLR4;MD2;OXLDL;肥胖;肾损伤;

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