Cyclophilin A and CD147 associate with progression of diabetic nephropathy

Cyclophilin A and CD147 associate with progression of diabetic nephropathy
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DOI:
10.1080/10715762.2018.1523545
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发表时间:
2018-12-02
影响因子:
3.3
通讯作者:
Liu, Chin-San
Liu, Chin-San
中科院分区:
生物学3区
文献类型:
--
作者:
Chiu, Ping-Fang;Su, Shih-Li;Liu, Chin-San

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探讨循环亲环蛋白A (CyP A)和CD147/EMMPRIN与2型糖尿病患者肾脏预后的关系及其可能的发病机制。自2004年以来,共招募了131名患者。在基线和每3个月测量糖化血红蛋白、血糖和尿白蛋白-肌酐比值水平。在基线时也测量血浆CyP A和CD147。根据基线血浆CyP A值中位数分为两组:< 93.64 ng/mL (A组,n = 65), >= 93.64 ng/mL (B组,n = 66)。每次随访时计算估计的肾小球滤过率。此外,当细胞暴露于葡萄糖或外源性CyP A或两者时,研究了细胞线粒体能量利用的线粒体功能测定。多因素分析,以中位水平(93.64)ng/mL作为临界值,显示基线时循环CyP A和CD147水平与基线估计肾小球滤过率(eGFR)相关(p = 0.042和p = 0.001)。纵向上,较高的基线血浆CyP A水平也与eGFR的快速下降相关(p = 0.016)。当使用连续血浆CyP A水平时,结果也具有显著性(p = 0.003)。在暴露于葡萄糖的细胞中,耗氧量(OCR)的结果显示基础呼吸、最大呼吸和ATP的产生显著降低。当与CyP A和葡萄糖同时孵育时,OCR进一步下降。血浆CyP A和CD147可作为2型糖尿病患者肾脏疾病进展的指标。
To find the associations of circulating cyclophilin A (CyP A) and CD147/EMMPRIN with renal outcomes in type 2 diabetes patients and possible pathogenesis involved. Total 131 patients were recruited since 2004. Glycated hemoglobin, blood glucose and urine albumin-creatinine ratio levels at baseline and every 3 months were measured. Plasma CyP A and CD147 were also measured at baseline. Patients were divided into two groups based upon the median level of the baseline plasma CyP A value: < 93.64 ng/mL (group A, n = 65), >= 93.64 ng/mL (group B, n = 66). The estimated glomerular filtration rate was calculated at each follow-up visit. Besides, mitochondrial function assay by cellular mitochondrial energy utility was studied when cells were exposed to glucose or exogenous CyP A or both. Multivariate analysis, using median level (93.64) ng/mL as the cut-off value, revealed that circulating CyP A and CD147 levels at baseline were associated with the baseline estimated glomerular filtration rate (eGFR) (p = .042 and p = .001 separately) in cross-sectional analysis. Longitudinally, higher baseline plasma CyP A level was also correlated to a rapid decline in eGFR (p = .016). The results were also significant when using the continuous plasma CyP A level (p = .003). In cells exposed to glucose, results of oxygen consumption rate (OCR) showed a significant reduction in basal respiration, maximal respiration and ATP production. Depressed OCR further occurred when incubated with both of CyP A and glucose. Plasma CyP A and CD147 can serve as indicators of renal disease progression in type 2 diabetes patients.