Dr. Hua Liu, Department of Nephrology, Xuan Wu Hospital, Capital Medical University, Beijing 100053, China, e-mail:
J Nutr Health Aging. 2020;24(3):246-250. doi: 10.1007/s12603-019-1302-y.
Recent studies have shown that hyperlipidemia is closely related to the progression of kidney disease and glomerulosclerosis has similar pathophysiological mechanisms with atherosclerosis. Atherosclerosis is essentially a chronic inflammatory process and various kidney diseases are characterized by a micro-inflammatory state. Hyperlipidemia levels are not parallel to the degree of glomerulosclerosis, inflammatory factors together with lipids may contribute to the pathogenesis of glomerulosclerosis. Therefore, it is key to clarify lipid-mediated renal injury through studying the mechanism by which inflammation affects cholesterol homeostasis at the cellular level. Intracellular lipid homeostasis involves both lipid uptake and excretion, therefore in this study, we aimed to explore whether interleukin-1β (IL-1β) promotes the uptake of oxidized low-density lipoprotein (Ox-LDL) to increase in intracellular lipid levels, and to clarify the effect of IL-1β on the expression of lectin-like oxidized LDL receptor 1 (LOX-1) and ATP-binding cassette transporter A1 (ABCA1), which may regulate cholesterol homeostasis in human mesangial cells (HMCs).
The effect of IL-1β on uptake of Ox-LDL labeled with fluorescent Dil (Dil-Ox-LDL) by HMCs was observed using laser confocal microscopy. The effect of IL-1β on LOX-1 and ABCA1 expression in HMCs was detected by polymerase chain reaction and western blotting.
Laser confocal microscopy revealed that HMCs took up Dil-Ox-LDL. Treatment of HMCs with 5 ng/ml IL-1β for 24 h significantly increased uptake of Dil-Ox-LDL. IL-1β also promoted LOX-1 mRNA and protein expression in a dose-dependent manner. Moreover, ABCA1 mRNA and protein expression were reduced by IL-1β in lipid-loaded HMCs in a dose-dependent manner.
IL-1β promotes the uptake of Ox-LDL and expression of LOX-1 in HMCs, whereas it inhibits expression of ABCA1 under lipid load. The imbalance in intracellular cholesterol resulted by IL-1β can in turn transform HMCs into foam cells and aggravate glomerulosclerosis.
最近的研究表明，高血脂与肾脏病的进展密切相关，肾小球硬化与动脉粥样硬化具有相似的病理生理机制。动脉粥样硬化本质上是一种慢性炎症过程，各种肾脏疾病的特征是微炎症状态。高血脂水平与肾小球硬化程度不成正比，炎症因子与脂质共同作用可能导致肾小球硬化的发病机制。因此，阐明炎症通过细胞水平影响胆固醇稳态的机制对于阐明脂质介导的肾损伤至关重要。细胞内脂质稳态涉及脂质摄取和排泄，因此在本研究中，我们旨在探讨白细胞介素-1β（IL-1β）是否促进氧化型低密度脂蛋白（Ox-LDL）的摄取，以增加细胞内脂质水平，并阐明 IL-1β对凝集素样 Ox-LDL 受体 1（LOX-1）和三磷酸腺苷结合盒转运体 A1（ABCA1）表达的影响，这可能调节人肾小球系膜细胞（HMC）中的胆固醇稳态。
通过激光共聚焦显微镜观察 IL-1β对 HMC 摄取荧光标记的 Ox-LDL（Dil-Ox-LDL）的影响。通过聚合酶链反应和蛋白质印迹法检测 IL-1β对 HMC 中 LOX-1 和 ABCA1 表达的影响。
激光共聚焦显微镜显示 HMC 摄取了 Dil-Ox-LDL。用 5 ng/ml IL-1β处理 HMC 24 h 可显著增加 Dil-Ox-LDL 的摄取。IL-1β还呈剂量依赖性促进 LOX-1 mRNA 和蛋白表达。此外，在脂质负载的 HMC 中，IL-1β 呈剂量依赖性降低 ABCA1 mRNA 和蛋白表达。
IL-1β促进 HMC 摄取 Ox-LDL 和 LOX-1 的表达，而在脂质负荷下抑制 ABCA1 的表达。IL-1β引起的细胞内胆固醇失衡反过来又可使 HMC 转化为泡沫细胞，加重肾小球硬化。
