Fibronectin in blood invokes the development of focal segmental glomerulosclerosis in mouse model.
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.
Shui
Hao-Ai
HA
Graduate Institute of Medical Sciences, Tri-Service General Hospital, National Defense Medical Center, No. 325, Sec. 2, Cheng-Gung Road, Taipei, Taiwan, ROC.
Ka
Shuk-Man
SM
Lin
Jung-Chen
JC
Lee
Jien-Huei
JH
Jin
Jong-Shiaw
JS
Lin
Yuh-Feng
YF
Sheu
Lai-Fa
LF
Chen
Ann
A
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005353:Fibronectins / Q000378:metabolism*; D005923:Glomerulosclerosis, Focal Segmental / Q000097:blood*; D007678:Kidney Glomerulus / Q000378:metabolism; D007834:Lasers; D051379:Mice; D008807:Mice, Inbred BALB C; D042282:Microdissection; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
D015415:Biomarkers; D005353:Fibronectins; D012333:RNA, Messenger; D003404:Creatinine