Wu Chung-Ze, Chang Li-Chien, Lin Yuh-Feng, Hung Yi-Jen, Pei Dee, Chen Jin-Shuen
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan ; Division of Endocrinology and Metabolism, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
School of Pharmacy, National Defense Medical Center, Taipei, Taiwan.
Dis Markers. 2015;2015:548101. doi: 10.1155/2015/548101. Epub 2015 Apr 5.
In cell model, we discovered the association between chaperonin-containing t-complex polypeptide 1 subunit β (TCP-1β) and early diabetic nephropathy (DN). In this study, we further explored the relationships between TCP-1β and type 2 diabetic mellitus (DM). To mimic the clinical hyperfiltration state, a type 2 DM mice model was established by feeding a high-fat diet in combination with treatment of streptozotocin and nicotinamide. Blood and urine were collected to determine creatinine clearance (C cr), and kidney tissues were harvested for evaluation of TCP-1β expression by immunohistochemistry and Western blot. Meanwhile, clinical subjects of healthy controls and type 2 DM were recruited to strengthen the evidence with urine TCP-1β. Results showed that C cr and the expression of TCP-1β in kidney were significantly higher one week after hyperglycemia development, suggesting that the hyperfiltration state was successfully established in the mice model. TCP-1β was expressed predominantly on renal tubules. By using the estimated glomerular filtration rate to index progression in clinical investigation, urine TCP-1β level was associated with the hyperfiltration phase in type 2 DM patients. Conclusively, we confirmed that TCP-1β is a possible biomarker for early nephropathy of type 2 DM, but further mechanistic study to elucidate its cause and pathway is needed.
在细胞模型中,我们发现了含伴侣蛋白的t复合体多肽1亚基β(TCP-1β)与早期糖尿病肾病(DN)之间的关联。在本研究中,我们进一步探讨了TCP-1β与2型糖尿病(DM)之间的关系。为模拟临床高滤过状态,通过高脂饮食联合链脲佐菌素和烟酰胺处理建立了2型糖尿病小鼠模型。采集血液和尿液以测定肌酐清除率(Ccr),并收集肾脏组织通过免疫组织化学和蛋白质免疫印迹法评估TCP-1β的表达。同时,招募健康对照和2型糖尿病的临床受试者以加强尿TCP-1β的证据。结果显示,高血糖发生一周后,小鼠的Ccr和肾脏中TCP-1β的表达显著升高,表明在小鼠模型中成功建立了高滤过状态。TCP-1β主要在肾小管上表达。在临床研究中,通过使用估计的肾小球滤过率来指示疾病进展,尿TCP-1β水平与2型糖尿病患者的高滤过阶段相关。总之,我们证实TCP-1β可能是2型糖尿病早期肾病的生物标志物,但需要进一步的机制研究来阐明其原因和途径。