Centre for Lipid Research, Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Second Affiliated Hospital, Chongqing Medical University, Chongqing, PR China.
Am J Physiol Renal Physiol. 2011 Oct;301(4):F713-22. doi: 10.1152/ajprenal.00341.2010. Epub 2011 Jul 27.
Both lipids and inflammation play important roles in the progression of kidney disease. This study was designed to investigate whether inflammation exacerbates lipid accumulation via LDL receptors (LDLr), thereby causing renal injury in C57BL/6J mice, apolipoprotein E (ApoE) knockout (KO) mice, and ApoE/CD36/scavenger receptor A triple KO mice. The mice were given a subcutaneous casein injection to induce inflammatory stress. After 14 wk, terminal blood samples were taken for renal function, lipid profiles, amyloid A (SAA), and IL-6 assays. Lipid accumulation in kidneys was visualized by oil red O staining. Fibrogenic molecule expression in kidneys was examined. There was a significant increase in serum SAA and IL-6 in the all casein-injected mice compared with respective controls. Casein injection reduced serum total cholesterol, LDL cholesterol, and HDL cholesterol and caused lipid accumulation in kidneys from three types of mice. The expression of LDLr and its regulatory proteins sterol-responsive element-binding protein (SREBP) 2 and SREBP cleavage-activating protein (SCAP) were upregulated in inflamed mice compared with controls. Casein injection induced renal fibrosis accompanied by increased expression of fibrogenic molecules in the triple KO mice. These data imply that inflammation exacerbates lipid accumulation in the kidney by diverting lipid from the plasma to the kidney via the SCAP-SREBP2-LDLr pathway and causing renal injury. Low blood cholesterol levels, resulting from inflammation, may be associated with high risk for chronic renal fibrosis.
脂质和炎症在肾脏病的进展中都起着重要作用。本研究旨在探讨炎症是否通过 LDL 受体（LDLr）加剧脂质积累，从而导致 C57BL/6J 小鼠、载脂蛋白 E（ApoE）基因敲除（KO）小鼠和 ApoE/CD36/清道夫受体 A 三重 KO 小鼠的肾脏损伤。给小鼠皮下注射酪蛋白以诱导炎症应激。14 周后，采集终末血样进行肾功能、血脂谱、淀粉样 A（SAA）和 IL-6 测定。通过油红 O 染色观察肾脏中的脂质积累。检查肾脏中纤维原性分子的表达。与各自的对照相比，所有酪蛋白注射小鼠的血清 SAA 和 IL-6 均显著增加。酪蛋白注射降低了血清总胆固醇、LDL 胆固醇和 HDL 胆固醇，并导致三种类型小鼠的肾脏脂质积累。与对照相比，炎症小鼠中 LDLr 及其调节蛋白固醇调节元件结合蛋白（SREBP）2 和 SREBP 切割激活蛋白（SCAP）的表达上调。酪蛋白注射诱导了三重 KO 小鼠的肾脏纤维化，同时伴有纤维原性分子表达增加。这些数据表明，炎症通过 SCAP-SREBP2-LDLr 途径将脂质从血浆转移到肾脏，从而加剧肾脏中的脂质积累，导致肾脏损伤。炎症引起的低血胆固醇水平可能与慢性肾脏纤维化的高风险相关。
