Inflammation-activated CXCL16 pathway contributes to tubulointerstitial injury in mouse diabetic nephropathy
Inflammation-activated CXCL16 pathway contributes to tubulointerstitial injury in mouse diabetic nephropathy
复制标题
炎症激活的CXCL16通路导致小鼠糖尿病肾病肾小管间质损伤
DOI：
10.1038/aps.2017.177
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发表时间：
2018-06-01
影响因子：
8.2
通讯作者：
Liu, Bi-cheng
中科院分区：
文献类型：
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作者：
Hu, Ze-bo;Ma, Kun-ling;Liu, Bi-cheng
炎症和血脂紊乱在协同加速糖尿病肾病进展中起着至关重要的作用。在这项研究中，我们研究了炎症和脂质紊乱如何在体内和体外引起糖尿病肾病的肾小管间质损伤。糖尿病db/db小鼠隔日皮下注射10%酪蛋白0.5mLsc，共8周，造成慢性炎症。与db/db小鼠相比，注射酪蛋白的db/db小鼠表现出严重的肾小管间质损伤，表现为细胞外基质(ECM)分泌增加和肾小管间质胆固醇积聚，并伴随着CXC趋化因子配体16(CXCL16)途径的激活。在体外实验中，我们用IL-1β(5 ng/m L)和高糖(30 m o l/L)处理HK-2细胞。IL-1β诱导HK-2细胞胆固醇蓄积，导致细胞内ROS生成、细胞外基质蛋白表达水平显著增加，并伴随CXCL16途径蛋白表达水平上调。反之，用小干扰RNA敲除HK-2细胞中的CXCL16后，IL-1β降解的变化减弱。结论：炎症通过增加CXCL16途径的活性，加速了小鼠糖尿病肾病肾小管间质的损害。
Inflammation and lipid disorders play crucial roles in synergistically accelerating the progression of diabetic nephropathy (DN). In this study we investigated how inflammation and lipid disorders caused tubulointerstitial injury in DN in vivo and in vitro. Diabetic db/db mice were injected with 10% casein (0.5 mL, sc) every other day for 8 weeks to cause chronic inflammation. Compared with db/db mice, casein-injected db/db mice showed exacerbated tubulointerstitial injury, evidenced by increased secretion of extracellular matrix (ECM) and cholesterol accumulation in tubulointerstitium, which was accompanied by activation of the CXC chemokine ligand 16 (CXCL16) pathway. In the in vitro study, we treated HK-2 cells with IL-1β (5 ng/mL) and high glucose (30 mmol/L). IL-1β treatment increased cholesterol accumulation in HK-2 cells, leading to greatly increased ROS production, ECM protein expression levels, which was accompanied by the upregulated expression levels of proteins in the CXCL16 pathway. In contrast, after CXCL16 in HK-2 cells was knocked down by siRNA, the IL-1β-deteriorated changes were attenuated. In conclusion, inflammation accelerates renal tubulointerstitial lesions in mouse DN via increasing the activity of CXCL16 pathway.