Identification of Novel Biomarker for Early Detection of Diabetic Nephropathy.
Identification of Novel Biomarker for Early Detection of Diabetic Nephropathy.
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DOI：
10.3390/biomedicines9050457
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发表时间：
2021-04-22
期刊：
影响因子：
4.7
通讯作者：
Kim HS
中科院分区：
文献类型：
--
作者：
Kim KS;Lee JS;Park JH;Lee EY;Moon JS;Lee SK;Lee JS;Kim JH;Kim HS
糖尿病肾病是糖尿病最常见的并发症之一。发生DN后，患者将进展为终末期肾病，这与高发病率和死亡率相关。在这里，我们开发了早期诊断生物标志物来检测DN作为DN干预的策略。对于DN模型，使用Zucker糖尿病肥胖大鼠进行DN表型分型。结果显示，DN大鼠血糖、血尿素氮（BUN）和血清肌酐水平显著升高，并伴有严重的肾损伤、纤维化和微结构改变。此外，DN大鼠显示肾损伤分子-1（KIM-1）和中性粒细胞明胶酶相关脂质运载蛋白（NGAL）的尿排泄显著增加。转录组分析显示，新的DN生物标志物，如互补成分4 b（C4 b），互补因子D（CFD），C-X-C基序趋化因子受体6（CXCR 6），白血病抑制因子（LIF）被确定。此外，在DN患者的尿液中也发现了它们。由于这些生物标志物在DN大鼠的尿液和肾脏以及糖尿病患者的尿液中均能检测到，因此所选的生物标志物可作为慢性糖尿病肾病的早期诊断生物标志物。
Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. After development of DN, patients will progress to end-stage renal disease, which is associated with high morbidity and mortality. Here, we developed early-stage diagnostic biomarkers to detect DN as a strategy for DN intervention. For the DN model, Zucker diabetic fatty rats were used for DN phenotyping. The results revealed that DN rats showed significantly increased blood glucose, blood urea nitrogen (BUN), and serum creatinine levels, accompanied by severe kidney injury, fibrosis and microstructural changes. In addition, DN rats showed significantly increased urinary excretion of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Transcriptome analysis revealed that new DN biomarkers, such as complementary component 4b (C4b), complementary factor D (CFD), C-X-C motif chemokine receptor 6 (CXCR6), and leukemia inhibitory factor (LIF) were identified. Furthermore, they were found in the urine of patients with DN. Since these biomarkers were detected in the urine and kidney of DN rats and urine of diabetic patients, the selected markers could be used as early diagnosis biomarkers for chronic diabetic nephropathy.
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