NDT Advance Access originally published online on March 30, 2006
Nephrology Dialysis Transplantation 2006 21(7):1794-1802; doi:10.1093/ndt/gfl113
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Original Articles: Experimental Nephrology
Fibronectin in blood invokes the development of focal segmental glomerulosclerosis in mouse model
1 Graduate Institute of Medical Sciences, 2 Department of Internal Medicine and 3 Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
Correspondence and offprint requests to: Dr Ann Chen, Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Cheng-Gung Road, Taipei, Taiwan, ROC. Email: doc31717{at}ndmctsgh.edu.tw
Background. 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.
Methods. 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.
Results. 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.
Conclusions. 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.
Keywords: adriamycin; biomarker; fibronectin; focal segmental glomerulosclerosis; laser microdissection
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