Summary: To investigate the expression and the role of three isoforms of Serum and Glucocorticoid-inducible Kinase (SGK) in experimental diabetic nephropathy (DN), 12 male C57BL/6 mice of 8-weeks-old were divided into two groups. Streptozotocin (STZ)-induced diabetic nephropathy and normal controls were analyzed at the end of the 4th week after the induction of diabetes. Renal hemodynamics and histological studies were performed. The expression of SGK1 mRNA, SGK2 mRNA and SGK3 mRNA of kidney cortex were measured by RT-PCR, and the cortical SGK1 protein was detected with Western blotting. Our results showed that the blood glucose, blood HbA1c, 24-h urinary protein, creatinine clearance and the renal index were all increased in DN group. More extracellular matrix (ECM) accumulation was observed. The level of cortical SGK1 mRNA and protein were up-regulated in DN group in comparison with control group. SGK2 and SGK3 mRNA were elevated in DN mice. In DN, mRNA level of three SGK isoforms and SGK1 protein were increased significantly. It is concluded that SGKs may contribute to the early renal injury of DN.
目的:研究血清和糖皮质激素诱导的蛋白激酶1(serum and glucocorticoid-inducible kinase1,SGK1)在糖尿病(DM)小鼠肾脏皮质中时间上差异性表达及意义。方法:采用链脲佐菌素(STZ)单次腹腔注射诱导小鼠糖尿病模型。将2月龄C57BL/6小鼠随机分成10组:第1、2、3、4、6、8、12周糖尿病小鼠组(DM1、DM2、DM3、DM4、DM6、DM8、DM12)和相应的第1、4、8周正常对照组(N1、N4、N8)。分别在DM模型制作成功后第1、2、3、4、6、8、12周末收集小鼠24h尿量,检测24h尿蛋白量;观察肾脏病理改变;半定量RT-PCR检测小鼠肾脏皮质SGK1及结缔组织生长因子(CTGF)mRNA的表达,Western blotting检测N4、DM4、DM8组皮质SGK1、CTGF蛋白的表达。结果:随着糖尿病病程的进展,DM组小鼠肾小球体积逐渐增大、系膜区逐渐增宽;DM组小鼠24h尿蛋白从第2周起开始逐渐增多,肾脏皮质SGK1mRNA表达从第2周开始明显上调,在第4周达到峰值。CTGF随着糖尿病病程的进展表达逐渐递增。结论:SGK1在糖尿病早期肾脏表达峰值的出现及CTGF持续递增的表达,提示SGK1在糖尿病肾病肾脏纤维化的发生发展过程中起重要作用。
