Journal Article

Fibronectin in blood invokes the development of focal segmental glomerulosclerosis in mouse model

Hao-Ai Shui, Shuk-Man Ka, Jung-Chen Lin, Jien-Huei Lee, Jong-Shiaw Jin, Yuh-Feng Lin, Lai-Fa Sheu and Ann Chen

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 21, issue 7, pages 1794-1802
Published in print July 2006 | ISSN: 0931-0509
Published online March 2006 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfl113
Fibronectin in blood invokes the development of focal segmental glomerulosclerosis in mouse model

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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

Journal Article.  4944 words.  Illustrated.

Subjects: Nephrology

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