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

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

doi:10.1093/ndt/gfi229

Cited by 43 publications

(57 citation statements)

References 21 publications

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“…In a murine model of crescentic lupus nephritis (chronic graft-versus-host disease), renal cortical and glomerular expression of lipocalin-2 was up-regulated after the induction of the disease (27). Moreover, urinary lipocalin-2 levels were increased in the mice up to 9 weeks after disease induction, coinciding with the presence of florid crescent formation.…”

Section: Discussionmentioning

confidence: 99%

Urinary lipocalin‐2 is associated with renal disease activity in human lupus nephritis

Pitashny¹,

Schwartz²,

Qing³

et al. 2007

Arthritis & Rheumatism

122

114

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Objective. Pathogenic monoclonal anti-doublestranded DNA (anti-dsDNA) antibodies up-regulate the expression of lipocalin-2 in glomerular mesangial cells. This study was undertaken to investigate whether polyclonal anti-dsDNA antibodies promote the local secretion of lipocalin-2 in the kidneys of patients with systemic lupus erythematosus (SLE), and whether urinary lipocalin-2 represents a marker of kidney involvement in SLE.Methods. Hispanic, African American, and white patients with SLE and normal healthy control subjects from affiliated hospitals of the Albert Einstein College of Medicine were recruited for this cross-sectional study. Patients were classified based on the presence of active renal disease according to the SLE Disease Activity Index (SLEDAI). Correlations of clinical and laboratory data with urinary and serum levels of lipocalin-2 were assessed.Results. Among SLE patients, urinary lipocalin-2 levels were significantly higher in those with lupus nephritis ( Conclusion. The high prevalence of LN in SLE patients and the prognostic significance of kidney disease support the need for identifying early biomarkers to assess the risk of nephritis development and for following up patients with established disease. These findings indicate that urinary lipocalin-2 is a potential marker of the presence and severity of renal involvement in adult patients with SLE.

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Section: Discussionmentioning

confidence: 99%

Urinary lipocalin‐2 is associated with renal disease activity in human lupus nephritis

Pitashny¹,

Schwartz²,

Qing³

et al. 2007

Arthritis & Rheumatism

122

114

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“…A murine ACGN model was induced in 7-to 8-wk-old (C57BL/6 ϫ DBA/2J) F1 hybrid mice by giving DBA/2J donor lymphocytes as described previously (17). Briefly, cell suspensions that contained a mixture of donor cells from the thymus, spleen, and lymph nodes (originating from the neck, axillary, and inguinal regions) were injected intravenously three times at 3-to 4-d intervals.…”

Section: Establishment Of Acgn Modelmentioning

confidence: 99%

“…Sections (4 m) were stained with hematoxylin and eosin. A semiquantitative evaluation for staining was performed as described previously (17).…”

Section: Clinical and Pathologic Evaluationmentioning

confidence: 99%

“…kit (Vector Laboratories, Burlingame, CA), or streptavidin-biotin peroxidase system (Dako) were then applied to the sections for 1 h. Sections were counterstained with hematoxylin or methyl green. Semiquantitative evaluations for staining were performed as described previously (15,17,18).…”

Section: Clinical and Pathologic Evaluationmentioning

confidence: 99%

“…Recently, we demonstrated that a murine chronic graft versus host disease can progress to an experimental ACGN that is characterized by extensive crescent formation in up to 80% of the glomeruli (17). This study tested whether blocking TGF-␤ signaling by overexpression of Smad7 is able to inhibit progressive renal injury that is induced immunologically in experimental ACGN.…”

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confidence: 99%

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Smad7 Gene Therapy Ameliorates an Autoimmune Crescentic Glomerulonephritis in Mice

Huang

Lan

et al. 2007

Journal of the American Society of Nephrology

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113

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Autoimmune crescentic glomerulonephritis is characterized by severe immune response with glomerular crescentic formation and fibrosis in the kidney. Recent studies indicate that overexpression of renal Smad7 attenuates both renal fibrosis and inflammation in rat remnant kidney. However, little attention has been paid to the potential role of TGF-␤/Smad signaling in autoimmune kidney disease. This study tested the hypothesis that blocking TGF-␤ signaling by overexpression of Smad7 may have a therapeutic effect in a mouse model of autoimmune crescentic glomerulonephritis that was induced in C57BL/6 ؋ DBA/2J F1 hybrid mice by giving DBA/2J donor lymphocytes. Smad7 gene was transfected into the kidney using the ultrasound-microbubble-mediated system. Results showed that overexpression of Smad7 blocked both renal fibrosis and inflammatory pathways in terms of Smad2/3 and NF-B activation (P < 0.01), thereby inhibiting ␣-smooth muscle actin; collagen I, III, and IV accumulation; and expression of inflammatory cytokines (IL-1␤ and IL-6), adhesion molecule/ chemokine (intercellular adhesion molecule-1, monocyte chemoattractant protein-1), and inducible nitric oxide synthase (all P < 0.01). Leukocyte infiltration (CD4 ؉ cells and macrophages) was also suppressed (P < 0.005). Severe histologic damage (glomerular crescent formation and tubulointerstitial injury) and functional injury including proteinuria were significantly improved (all P < 0.05). This study provides important evidence that overexpression of Smad7 may have therapeutic potential for autoimmune kidney disease.

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Neutrophil gelatinase–associated lipocalin is a predictor of the course of global and renal childhood‐onset systemic lupus erythematosus disease activity

Hinze¹,

Suzuki²,

Klein‐Gitelman³

et al. 2009

Arthritis & Rheumatism

129

116

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Objective. To determine whether neutrophil gelatinase-associated lipocalin (NGAL) can predict worsening of global and renal disease activity in childhood-onset systemic lupus erythematosus (SLE).Methods. One hundred eleven patients with childhood-onset SLE were enrolled in a longitudinal, prospective study with quarterly study visits and had at least 3 study visits. At each visit, global disease activity was measured using 3 external standards: the numerically converted British Isles Lupus Assessment Group (BILAG) index, the SLE Disease Activity Index 2000 update score, and the physician's assessment of global disease activity. Renal and extrarenal disease activity were measured by the respective domain scores. The disease course over time was categorized at the most recent visit (persistently active, persistently inactive, improved, or worsening). Plasma and urinary NGAL levels were measured by enzyme-linked immunosorbent assay, and urinary NGAL levels were standardized to the urinary creatinine concentration. The longitudinal changes in NGAL levels were compared with the changes in SLE disease activity using mixed-effect models.Results. Significant increases in standardized urinary NGAL levels of up to 104% were detected up to 3 months before worsening of lupus nephritis (as measured by all 3 external standards). Plasma NGAL levels increased significantly by as much as 26% up to 3 months before worsening of global SLE disease activity as measured by all 3 external standards. Plasma NGAL levels increased significantly by 26% as early as 3 months prior to worsening of lupus nephritis as measured by the BILAG renal score.Conclusion. Serial measurement of urinary and plasma NGAL levels may be valuable in predicting impending worsening of global and renal childhoodonset SLE disease activity.

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

Abstract: 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.

Cited by 43 publications

References 21 publications

Urinary lipocalin‐2 is associated with renal disease activity in human lupus nephritis

Urinary lipocalin‐2 is associated with renal disease activity in human lupus nephritis

Smad7 Gene Therapy Ameliorates an Autoimmune Crescentic Glomerulonephritis in Mice

Neutrophil gelatinase–associated lipocalin is a predictor of the course of global and renal childhood‐onset systemic lupus erythematosus disease activity

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