Oral interferon-α treatment of mice with cryoglobulinemic glomerulonephritis

Segerer, Stephan; Hudkins, Kelly L.; Taneda, Sekiko; Wen, Ming‐Shien; Cui, Yan; Segerer, Manuela; Farr, Andrew G.; Alpers, Charles E.

doi:10.1053/ajkd.2002.32011

Cited by 17 publications

(17 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Tissue fixed in half-strength Karnovsky's solution was processed, embedded, stained, and examined according to standard protocols as previously published (11).…”

Section: Methodsmentioning

confidence: 99%

A new function for parietal epithelial cells: a second glomerular barrier

Ohse

Chang

Pippin

et al. 2009

American Journal of Physiology-Renal Physiology

Self Cite

View full text Add to dashboard Cite

The functional role of glomerular parietal epithelial cells (PECs) remains poorly understood. To test the hypothesis that PECs form an impermeable barrier to filtered protein through the formation of tight junctions (TJ), studies were performed in normal animals and in the anti-glomerular basement membrane (GBM) model of crescentic nephritis. Electron microscopy showed well-defined TJ between PECs in normal mice, which no longer could be identified when these cells became extensively damaged or detached from their underlying Bowman's basement membrane. The TJ proteins claudin-1, zonula occludens-1, and occludin stained positive in PECs; however, staining decreased in anti-GBM disease. To show that these events were associated with increased permeability across the PEC-Bowman's basement membrane barrier, control and diseased animals were injected intravenously with either Texas red-conjugated dextran (3 kDa) or ovalbumin (45 kDa) tracers. As expected, both tracers were readily filtered across the glomerular filtration barrier and taken up by proximal tubular cells. However, when the glomerular filtration barrier was injured in anti-GBM disease, tracers were taken up by podocytes and PECs. Moreover, tracers were also detected between PECs and the underlying Bowman's basement membrane, and in many instances were detected in the extraglomerular space. We propose that together with its underlying

show abstract

“…Tissue fixed in half-strength Karnovsky's solution was processed, embedded, stained, and examined according to standard protocols as previously published (11).…”

Section: Methodsmentioning

confidence: 99%

A new function for parietal epithelial cells: a second glomerular barrier

Ohse

Chang

Pippin

et al. 2009

American Journal of Physiology-Renal Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Sections were counterstained with periodic acid Schiff/methyl-green, dehydrated and coverslipped. Macrophages were detected using a rat anti-mouse MAC-2 antibody as previously described [24](Cederlane, Ontario, Canada) and a mouse-adsorbed anti-rat antibody was utilized as secondary anti-body (Vector Laboratories). A monoclonal mouse IgG2a antibody was used for detection of mesangial α-smooth muscle actin expression (as previously described [25]) (clone 1A4, DAKO, Carpinteria, Calif., USA).…”

Section: Methodsmentioning

confidence: 99%

Hyperglycemia and Hyperlipidemia Act Synergistically to Induce Renal Disease in LDL Receptor-Deficient BALB Mice

Spencer¹,

Mühlfeld

Segerer

et al. 2004

Am J Nephrol

Self Cite

View full text Add to dashboard Cite

Diabetic nephropathy is the leading cause of end-stage renal disease in Western countries, but only a portion of diabetic patients develop diabetic nephropathy. Dyslipidemia represents an important aspect of the metabolic imbalance in diabetic patients. In this study, we addressed the impact of combined hyperlipidemia and hyperglycemia on renal pathology. Kidneys from wild-type (WT) or LDL receptor-deficient BALB/cBy mice (BALB.LDLR–/–) were examined at 22 weeks of age. Diabetes was induced by administration of streptozotocin and mice were randomly assigned to either standard chow or Western diet. Chow fed BALB.LDLR–/– mice did not demonstrate renal abnormalities, whereas BALB. LDLR–/– mice fed a Western diet showed occasional glomerular and tubulointerstitial foam cells. Diabetic WT mice had modestly increased glomerular cellularity and extracellular matrix. Hyperlipidemic and diabetic BALB.LDLR–/– mice exhibited an increase in glomerular cellularity and extracellular matrix, accumulation of glomerular and tubulointerstitial foam cells and mesangial lipid deposits. The tubular epithelium demonstrated pronounced lipid induced tubular degeneration with increased tubular epithelial cell turnover. Hyperlipidemia and hyperglycemia seem to act synergistically in inducing renal injury in the BALB.LDLR–/– mouse. This model of diabetic nephropathy is unique in its development of tubular lesions and may represent a good model for hyperlipidemia-exacerbated diabetic nephropathy.

show abstract

“…CD3-, ER-HR3-, Mac-2-, and Ki-67-positive cells were detected using 4-m-thick paraffin sections from renal tissue (17,18). IgG of the corresponding isotype served as negative control.…”

Section: Immunofluorescence and Immunohistochemistrymentioning

confidence: 99%

Chemokine Receptor Ccr2 Deficiency Reduces Renal Disease and Prolongs Survival in MRL/lpr Lupus-Prone Mice

Lema

Maier²,

Franz³

et al. 2005

Journal of the American Society of Nephrology

Self Cite

View full text Add to dashboard Cite

MRL/MpJ-Faslpr /J (MRL/lpr) mice represent a well-established mouse model of human systemic lupus erythematosus. MRL/lpr mice homozygous for the spontaneous lymphoproliferation mutation (lpr) are characterized by systemic autoimmunity, massive lymphadenopathy associated with proliferation of aberrant T cells, splenomegaly, hypergammaglobulinemia, arthritis, and fatal immune complex-mediated glomerulonephritis. It was reported previously that steady-state mRNA levels for the chemokine (C-C motif) receptor 2 (Ccr2) continuously increase in kidneys of MRL/lpr mice. For examining the role of Ccr2 for development and progression of immune complex-mediated glomerulonephritis, Ccr2-deficient mice were generated and backcrossed onto the MRL/lpr genetic background. Ccr2-deficient MRL/lpr mice developed less lymphadenopathy, had less proteinuria, had reduced lesion scores, and had less infiltration by T cells and macrophages in the glomerular and tubulointerstitial compartment. Ccr2-deficient MRL/lpr mice survived significantly longer than MRL/lpr wild-type mice despite similar levels of circulating immunoglobulins and comparable immune complex depositions in the glomeruli of both groups. Anti-dsDNA antibody levels, however, were reduced in the absence of Ccr2. The frequency of CD8 ؉ T cells in peripheral blood was significantly lower in Ccr2-deficient MRL/lpr mice. Thus Ccr2 deficiency influenced not only monocyte/ macrophage and T cell infiltration in the kidney but also the systemic T cell response in MRL/lpr mice. These data suggest an important role for Ccr2 both in the general development of autoimmunity and in the renal involvement of the lupus-like disease. These results identify Ccr2 as an additional possible target for the treatment of lupus nephritis.

show abstract

Oral interferon-α treatment of mice with cryoglobulinemic glomerulonephritis

Cited by 17 publications

References 33 publications

A new function for parietal epithelial cells: a second glomerular barrier

A new function for parietal epithelial cells: a second glomerular barrier

Hyperglycemia and Hyperlipidemia Act Synergistically to Induce Renal Disease in LDL Receptor-Deficient BALB Mice

Chemokine Receptor Ccr2 Deficiency Reduces Renal Disease and Prolongs Survival in MRL/lpr Lupus-Prone Mice

Contact Info

Product

Resources

About