Glomerular crescent-related biomarkers in a murine model of chronic graft versus host disease.
BACKGROUND
We examined the alterations in gene expression associated with the development of crescentic glomerulonephritis in murine chronic graft-versus-host disease, a model for human systemic lupus erythematosus.


METHODS
The disease was induced in (C57BL/6 x DBA/2) F(1) hybrids by injection of DBA/2 lymphocytes leading to deposition of auto-antibodies in the glomeruli, and a lupus type of nephritis morphologically. After extensive crescent formation at week 9 of disease, cDNA microarray analysis was performed and highly expressed genes were evaluated as molecular markers by real-time reverse transcription-polymerase chain reaction (RT-PCR), in situ hybridization, immunohistochemistry and immunoassay of urine proteins.


RESULTS
Six genes, secreted acidic cysteine-rich glycoprotein (Sparc), thymosin beta 10 (Tmsb10), S100 calcium-binding protein A6 (S100a6), annexin A2 (Anxa2), osteopontin (OPN) and lipocalin 2 (Lcn2), were quantified by real-time RT-PCR in laser microdissected glomeruli in a time course manner. Sparc was detected early before the onset of proteinuria and continued to increase throughout the course of the disease. The expression of Tmsb10, S100a6 and Anxa2 coincided with heavy proteinuria. By week 9, OPN and Lcn2 were highly expressed. The expression of proteins encoded by these genes was predominant in the glomerular crescent. The protein levels of Sparc, OPN and Lcn2 in urine were significantly elevated.


CONCLUSIONS
These findings implicate these six genes in the development of glomerular crescents. More importantly, detection of Sparc, OPN and Lcn2 in urine may mean that these molecules could serve as important biomarkers for non-invasive diagnosis of glomerular crescents.
Ka
Shuk-Man
SM
Graduate Institute of Life Sciences, Tri-Service General Hospital, Taipei, Taiwan, Republic of China.
Rifai
Abdalla
A
Chen
Jan-Hen
JH
Cheng
Chao-Wen
CW
Shui
Hao-Ai
HA
Lee
Herng-Sheng
HS
Lin
Yuh-Feng
YF
Hsu
Lai-Fa
LF
Chen
Ann
A
D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D015870:Gene Expression; D006086:Graft vs Host Disease / Q000150:complications*; D008181:Lupus Nephritis / Q000209:etiology* / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA