NDT Advance Access published online on March 30, 2006
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfl113
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1 Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, ROC
* To whom correspondence should be addressed. 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.
Received December 19, 2005
Accepted February 22, 2006
Original Article
Fibronectin in blood invokes the development of focal segmental glomerulosclerosis in mouse model
Hao-Ai Shui 1,
Shuk-Man Ka 2,
Jung-Chen Lin 2,
Jien-Huei Lee 2,
Jong-Shiaw Jin 2,
Yuh-Feng Lin 3,
Lai-Fa Sheu 2,
and
Ann Chen 2 *
2 Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC
3 Department of Internal Medicine, National Defense Medical Center, Taipei, Taiwan, ROC
Ann Chen, E-mail: doc31717{at}ndmctsgh.edu.tw
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