Glomerular crescent-related biomarkers in a murine model of chronic graft versus host disease

Shuk Man Ka, Abdalla Rifai, Jan Hen Chen, Chao Wen Cheng, Hao Ai Shui, Herng Sheng Lee, Yuh Feng Lin, Lai Fa Hsu, Ann Chen

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

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/6X DBA/2) F1 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.

Original languageEnglish
Pages (from-to)288-298
Number of pages11
JournalNephrology Dialysis Transplantation
Volume21
Issue number2
DOIs
Publication statusPublished - Feb 2006
Externally publishedYes

Fingerprint

Osteopontin
Graft vs Host Disease
Biomarkers
Urine
Proteinuria
Reverse Transcription
Annexin A6
Annexin A2
Genes
Polymerase Chain Reaction
Lupus Nephritis
Proteins
Calcium-Binding Proteins
Microarray Analysis
Glomerulonephritis
Oligonucleotide Array Sequence Analysis
Immunoassay
Systemic Lupus Erythematosus
In Situ Hybridization
Cysteine

Keywords

  • Anxa2
  • Crescentic lupus nephritis
  • Laser microdissection
  • S100a6
  • Sparc
  • Tmsb10

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

Glomerular crescent-related biomarkers in a murine model of chronic graft versus host disease. / Ka, Shuk Man; Rifai, Abdalla; Chen, Jan Hen; Cheng, Chao Wen; Shui, Hao Ai; Lee, Herng Sheng; Lin, Yuh Feng; Hsu, Lai Fa; Chen, Ann.

In: Nephrology Dialysis Transplantation, Vol. 21, No. 2, 02.2006, p. 288-298.

Research output: Contribution to journalArticle

Ka, Shuk Man ; Rifai, Abdalla ; Chen, Jan Hen ; Cheng, Chao Wen ; Shui, Hao Ai ; Lee, Herng Sheng ; Lin, Yuh Feng ; Hsu, Lai Fa ; Chen, Ann. / Glomerular crescent-related biomarkers in a murine model of chronic graft versus host disease. In: Nephrology Dialysis Transplantation. 2006 ; Vol. 21, No. 2. pp. 288-298.
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abstract = "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/6X DBA/2) F1 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.",
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AU - Rifai, Abdalla

AU - Chen, Jan Hen

AU - Cheng, Chao Wen

AU - Shui, Hao Ai

AU - Lee, Herng Sheng

AU - Lin, Yuh Feng

AU - Hsu, Lai Fa

AU - Chen, Ann

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N2 - 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/6X DBA/2) F1 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.

AB - 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/6X DBA/2) F1 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.

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