Shui Hao-Ai, Ka Shuk-Man, Lin Jung-Chen, Lee Jien-Huei, Jin Jong-Shiaw, Lin Yuh-Feng, Sheu Lai-Fa, Chen Ann
Graduate Institute of Medical Sciences, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Cheng-Gung Road, Taipei, Taiwan, ROC.
Nephrol Dial Transplant. 2006 Jul;21(7):1794-802. doi: 10.1093/ndt/gfl113. Epub 2006 Mar 30.
Focal segmental glomerulosclerosis (FSGS) is caused by gradual deposition of extracellular matrix proteins, one of which, fibronectin (FN) is critical for sclerosis development. The origin of the FN deposited at an early stage of FSGS is still unclear.
For investigating the origin of FN, the onset of increases in FN levels in the serum, glomeruli and urine were studied in a mouse model induced by adriamycin and compared with the time-course of development of glomerulosclerosis and expression of FN mRNA.
In the FSGS mice, serum FN levels were significantly increased as early as the onset of proteinuria on day 4 (7.26 +/- 0.37 mg/ml compared with 5.58 +/- 0.76 mg/ml in normal controls, P < 0.05). This was followed by an increase in glomerular deposition of FN protein on day 7 (FN/actin ratio, 0.216 +/- 0.003 compared with 0.039 +/- 0.009 in normal controls, P < 0.05). Glomerular m-RNA expression was also significantly elevated on day 7, but the locally synthesized FN did not show any increase until day 15. A significant increase in urinary FN protein and focal glomerulosclerosis was seen on day 11.
We infer that FN in blood acts as an initiator of the development of FSGS in this mouse model. In addition, serum and urine FN proteins could serve as useful biomarkers for monitoring the progression of FSGS.
局灶节段性肾小球硬化（FSGS）是由细胞外基质蛋白逐渐沉积所致，其中纤连蛋白（FN）对硬化发展至关重要。FSGS早期沉积的FN来源仍不清楚。
为研究FN的来源，在阿霉素诱导的小鼠模型中研究血清、肾小球和尿液中FN水平升高的起始情况，并与肾小球硬化发展的时间进程和FN mRNA表达进行比较。
在FSGS小鼠中，血清FN水平早在第4天蛋白尿发作时就显著升高（7.26±0.37mg/ml，而正常对照组为5.58±0.76mg/ml，P<0.05）。随后在第7天FN蛋白的肾小球沉积增加（FN/肌动蛋白比值，0.216±0.003，而正常对照组为0.039±0.009，P<0.05）。肾小球mRNA表达在第7天也显著升高，但局部合成的FN直到第15天才显示出增加。在第11天观察到尿FN蛋白和局灶性肾小球硬化显著增加。
我们推断血液中的FN在该小鼠模型中作为FSGS发展的启动因子。此外，血清和尿FN蛋白可作为监测FSGS进展的有用生物标志物。
