Inflammatory stress exacerbates lipid accumulation and podocyte injuries in diabetic nephropathy
Inflammatory stress exacerbates lipid accumulation and podocyte injuries in diabetic nephropathy
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炎症应激加剧糖尿病肾病的脂质积累和足细胞损伤
DOI：
10.1007/s00592-015-0753-9
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发表时间：
2015-04
影响因子：
3.8
通讯作者：
Ma KL
中科院分区：
文献类型：
--
作者：
Zhang Yang;Ma Kun Ling;Liu Jing;Wu Yu;Hu Ze Bo;Liu Liang;Lu Jian;Zhang Xiao Liang;Liu Bi Cheng;Ma KL
目的糖尿病肾病（Diabetic nephropathy，DN）是一种慢性炎症性疾病，伴有不同程度的血脂紊乱。本研究旨在确定炎症应激是否加剧足细胞中的脂质积聚，并探讨其在DN中的潜在机制，使用体外和体内study.MethodsWe使用IL-1β刺激足细胞在体外和酪蛋白注射在db/db小鼠体内诱导炎症应激。采用酶联免疫吸附试验测定血清炎性细胞因子的血浆水平。采用病理染色和电镜观察肾脏病理变化。通过油红O染色和胆固醇定量测定来评价细胞内脂质积聚。细胞外基质蛋白，足细胞损伤的生物标志物，参与LDLr通路的分子的基因和蛋白质表达水平进行了评估，使用免疫荧光染色，实时PCR，和western blot analysis.ResultsIncreased血浆水平的炎症细胞因子在酪蛋白注射db/db小鼠表示成功诱导的发炎DN模型。肾脏形态学改变、足细胞损伤和上皮间质转化（EMT）在注射酪蛋白的db/db小鼠中更为显著。此外，炎症增加了db/db小鼠肾脏中的脂滴积聚，这是由于db/db小鼠肾脏中LDLr、固醇调节元件结合蛋白（SREBP）裂解激活蛋白（SCAP）和SREBP-2的蛋白表达水平增加所致。体外研究进一步证明，炎症增加了足细胞中的脂质积累并诱导足细胞EMT，这与炎症介导的LDLr、SCAP和SREBP-2表达水平的增加相关，增加SCAP/SREBP-结论炎症通过内质网和高尔基体介导足细胞的脂质积聚和EMT，从而诱导足细胞的EMT。LDLr通路的失调，其导致足细胞损伤并加速DN的进展。
AimsDiabetic nephropathy (DN) is a chronic inflammatory disease that is accompanied by different degrees of lipid disorders. The present study was conducted to determine whether inflammatory stress exacerbates lipid accumulation in podocytes and to investigate its underlying mechanisms in DN using in vitro and in vivo studies.MethodsWe used IL-1β stimulation in podocytes in vitro and casein injections in db/db mice in vivo to induce inflammatory stress. The plasma levels of serum inflammatory cytokines were determined using an enzyme-linked immunosorbent assay. The renal pathology was evaluated using pathological staining and electron microscopy. Intracellular lipid accumulation was evaluated by Oil Red O staining and a cholesterol quantitative assay. The gene and protein expression levels of extracellular matrix proteins, biomarkers of podocyte injury, and molecules involved in the LDLr pathway were evaluated using immunofluorescence staining, real-time PCR, and western blot analysis.ResultsIncreased plasma levels of inflammatory cytokines in the casein-injected db/db mice indicated a successful induction of the inflamed DN model. The kidney morphological changes, podocyte injury, and epithelial mesenchymal transition (EMT) were more significant in casein-injected db/db mice. Moreover, inflammation increased the lipid droplet accumulation in the kidneys of db/db mice, which resulted from the increased protein expression levels of LDLr, sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP), and SREBP-2 in the kidneys of db/db mice. The in vitro studies further demonstrated that inflammation increased the lipid accumulation in the podocytes and induced podocyte EMT, which were correlated with inflammation-mediated increases in the expression levels of LDLr, SCAP, and SREBP-2, and increased translocation of the SCAP/SREBP-2 complex from the endoplasmic reticulum to the Golgi in the podocytes.ConclusionInflammation induced lipid accumulation and the EMT of podocytes through the dysregulation of the LDLr pathway, which contributed to podocyte injury and accelerated the progression of DN.
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影响因子：
3.6
作者：
Ma KL;Ni J;Wang CX;Liu J;Zhang Y;Wu Y;Lv LL;Ruan XZ;Liu BC
通讯作者：
Liu BC
影响因子：
3
作者：
R. Atkins;P. Zimmet
通讯作者：
R. Atkins;P. Zimmet
影响因子：
3.8
作者：
Robert C Atkins;P. Zimmet
通讯作者：
Robert C Atkins;P. Zimmet
影响因子：
9.2
作者：
Ma KL;Zhang Y;Liu J;Wu Y;Hu ZB;Ruan XZ;Liu BC
通讯作者：
Liu BC
影响因子：
6
作者：
Li, Yingjian;Kang, Young Sun;Liu, Youhua
通讯作者：
Liu, Youhua