scholarly journals Fibronectin mRNA and protein accumulation, distribution, and breakdown in rabbit anti-glomerular basement membrane disease.

1991 ◽  
Vol 1 (12) ◽  
pp. 1334-1342
Author(s):  
M Goyal ◽  
R Wiggins
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Matrix Protein ◽  
Interstitial Fibrosis ◽  
Early Time ◽  
Protein Accumulation ◽  
Glomerular Injury ◽  
Crescent Formation ◽  
Mesangial Area ◽  
Fibronectin Mrna

Fibronectin is a multifunctional matrix protein which by immunofluorescence appears to be present in increased amounts during glomerular injury. To examine fibronectin metabolism in glomerular injury, an anti-glomerular basement membrane model that progresses to severe glomerular crescent formation, glomerulosclerosis, and interstitial fibrosis was used. Fibronectin was purified from rabbit plasma, and a monoclonal antibody raised against rabbit fibronectin was used for immunolocalization and quantitation of fibronectin protein. RNA and protein were extracted from isolated glomeruli and whole renal cortex at various times during progression of disease. At day 4, there was a 2.5-fold increase in fibronectin protein which by immunofluorescence appeared to be in the glomerular mesangial area. There was no increase in glomerular fibronectin mRNA at this time. This discrepancy is consistent with the conclusion that, at this early time point, the increased glomerular fibronectin comes predominantly from plasma. By day 7, glomerular fibronectin mRNA and extractable fibronectin protein were increased in association with bright immunofluorescence along the inner aspect of Bowman's capsule where early crescents were forming. Similarly, at day 14, crescents stained very brightly for fibronectin. These results are consistent with the conclusion that, at later time points, fibronectin is synthesized in glomeruli in association with cell division and crescent formation. Degradation of fibronectin in glomerular and cortical extracts was demonstrated under normal and nephritic conditions by finding fibronectin proteolytic fragmentation by Western blot.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Fibronectin mRNA in the developing glomerular crescent in rabbit antiglomerular basement membrane disease.

1995 ◽  
Vol 5 (12) ◽  
pp. 2087-2090
Author(s):  
S P Sady ◽  
M Goyal ◽  
P E Thomas ◽  
B L Wharram ◽  
R C Wiggins
Keyword(s):  
Wound Healing ◽  
In Situ Hybridization ◽  
Basement Membrane ◽  
Matrix Protein ◽  
Crescent Formation ◽  
Plasma Phase ◽  
Two Phases ◽  
Fibronectin Mrna ◽  
In Cells

Fibronectin is a multifunctional matrix protein important in wound healing that is markedly increased in glomerular crescents. A previous report established two phases of fibronectin metabolism in crescent formation in an anti-glomerular basement membrane model of crescentic nephritis in the rabbit. Phase I was associated with increased glomerular fibronectin content from plasma. Phase II was associated with increased fibronectin mRNA in glomeruli. To examine the hypothesis that fibronectin is synthesized in the developing crescent, rabbit fibronectin cDNA was cloned, sense and antisense riboprobes were prepared and their specificity under the conditions to be used was validated and in situ hybridization studies were performed in the model. The results showed that the cells in the developing glomerular crescent express an intense fibronectin mRNA signal at Day 7 and that this signal persisted in cells of the crescent at Day 14. This result shows that fibronectin synthesis does indeed take place in cells of the developing crescent in this model and supports the hypothesis that fibronectin may be an important agent regulating crescent formation and fibrosis.

scholarly journals Suppression of anti-glomerular basement membrane nephritis by administration of anti-monocyte chemoattractant protein-1 antibody in WKY rats.

1997 ◽  
Vol 8 (7) ◽  
pp. 1174-1178
Author(s):  
H Fujinaka ◽  
T Yamamoto ◽  
M Takeya ◽  
L Feng ◽  
K Kawasaki ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Cross Section ◽  
Glomerular Basement Membrane ◽  
Suppressive Effect ◽  
Glomerular Injury ◽  
Crescent Formation ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein ◽  
Wky Rats

Anti-glomerular basement membrane (GBM) nephritis in WKY rats is characterized by an accumulation of CD8-positive lymphocytes (CD8+ lym) and monocytes/macrophages (Mo/M psi) in the glomeruli and crescent formation. In the study presented here, the involvement of a chemokine for Mo/M psi, monocyte chemoattractant protein-1 (MCP-1), was examined in this model. An intense induction of mRNA for MCP-1 in the glomeruli and a suppressive effect of anti-MCP-1 antibody administration on the glomerular Mo/M psi accumulation and proteinuria were found. MCP-1 mRNA was expressed intensely in the glomeruli 4 d after the anti-GBM antibody injection. When MCP-1 was neutralized with anti-MCP-1 antibody administration, the number of Mo/M psi infiltrating in the glomeruli decreased by 34.7% (19.6 +/- 7.1 versus 30.0 +/- 6.0 per glomerular cross-section, P < 0.01) and proteinuria by 66.2% (15.6 +/- 9.3 versus 46.1 +/- 15.1 mg/d, P < 0.01) at day 4. In contrast, the number of CD8+ lym accumulating in the glomeruli was not affected significantly (6.6 +/- 2.7 versus 6.0 +/- 3.0 per glomerular cross-section, P > 0.05). However, the treatment with the anti-MCP-1 antibody did not reduce Mo/M psi infiltration, urinary protein excretion, and crescent formation at day 8. These data suggest that MCP-1 plays a role in the glomerular accumulation of Mo/M psi, and that the infiltrating Mo/M psi cause glomerular injury and increased excretion of protein in the urine.

Ovine Mesangiocapillary Glomerulonephritis Type I and Crescent Formation

1990 ◽  
Vol 27 (1) ◽  
pp. 26-34 ◽  
Author(s):  
P. F. Frelier ◽  
D. L. Armstrong ◽  
J. Pritchard
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Inflammatory Cells ◽  
Suitable Model ◽  
Type I ◽  
Human Beings ◽  
Crescent Formation ◽  
Mesangiocapillary Glomerulonephritis ◽  
Bowman's Capsule

Morphologic examination of four Finnish Landrace mixed-breed lambs, 27 to 35 days of age, affected with mesangiocapillary glomerulonephritis type 1, demonstrated a progressive glomerulonephritis. By 27 days of age, three lambs had crescents in 58 to 93% of glomeruli. These three lambs were also uremic. The accelerated rate of crescent formation was attributed to infiltrating polymorphonuclear leukocytes and monocytes, the result of discontinuities (gaps) in the glomerular basement membrane, and to the loss of the integrity of Bowman's capsule. In the three lambs, platelets were identified adjacent to the endothelium or denuded glomerular basement membrane. Two distinctly different types of crescents were noted, apparently dependent on the integrity of Bowman's capsule. One type resulted from the influx of inflammatory cells and dissociation of parietal epithelial cells from Bowman's capsule. The other type was more extensive and contained collagen and was associated with damage to Bowman's capsule resulting in cellular infiltration from the interstitium and sclerosis. Based on morphologic similarities, ovine mesangiocapillary glomerulonephritis is a suitable model for studying the pathogenesis and treatment of mesangiocapillary glomerulonephritis type 1 in human beings.

scholarly journals Growth Differentiation Factor 15 Ameliorates Anti-Glomerular Basement Membrane Glomerulonephritis in Mice

2020 ◽  
Vol 21 (19) ◽  
pp. 6978
Author(s):  
Foteini Moschovaki-Filippidou ◽  
Stefanie Steiger ◽  
Georg Lorenz ◽  
Christoph Schmaderer ◽  
Andrea Ribeiro ◽  
...  
Keyword(s):  
T Cells ◽  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Transforming Growth Factor ◽  
Protective Effects ◽  
Crescent Formation ◽  
Activated T Cells ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
Deficient Mice

Growth differentiation factor 15 (GDF15) is a member of the transforming growth factor-β (TGF-β) cytokine family and an inflammation-associated protein. Here, we investigated the role of GDF15 in murine anti-glomerular basement membrane (GBM) glomerulonephritis. Glomerulonephritis induction in mice induced systemic expression of GDF15. Moreover, we demonstrate the protective effects for GDF15, as GDF15-deficient mice exhibited increased proteinuria with an aggravated crescent formation and mesangial expansion in anti-GBM nephritis. Herein, GDF15 was required for the regulation of T-cell chemotactic chemokines in the kidney. In addition, we found the upregulation of the CXCR3 receptor in activated T-cells in GDF15-deficient mice. These data indicate that CXCL10/CXCR3-dependent-signaling promotes the infiltration of T cells into the organ during acute inflammation controlled by GDF15. Together, these results reveal a novel mechanism limiting the migration of lymphocytes to the site of inflammation during glomerulonephritis.

Mechanisms of glomerular injury

2015 ◽  
Author(s):  
Neil Turner
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Inflammatory Diseases ◽  
Calcineurin Inhibitors ◽  
Inflammatory Cells ◽  
Renal Diseases ◽  
Direct Effects ◽  
Glomerular Injury ◽  
Wide Range

Proteinuric diseases, historically termed ‘nephrosis’, are characterized by subtle abnormalities in podocytes or by abnormal glomerular matrix, including the scarring laid down by inflammatory diseases. Angiotensin blockers, corticosteroids, calcineurin inhibitors, and a wide range of other drugs known or believed to be effective in different renal diseases, appear to have direct effects on podocytes that reduce proteinuria that may be important to their effectiveness. Several of these have previously been assumed to work via haemodynamic, immune or other modes. Haematuric diseases are characterized by inflammatory disruption of the glomerular basement membrane (GBM) (‘nephritis’), or less commonly by fragile GBM without inflammation. The majority of haematuric conditions are slowly or rapidly destructive diseases associated with infiltration of inflammatory cells, and proliferation of endogenous cells of the glomerulus, probably in attempts at repair. With time, many haematuric diseases are associated with the development of proteinuria, possibly as a consequence of scarring and its effects on podocyte function.

(Pro)renin receptor promotes crescent formation via the ERK1/2 and Wnt/β-catenin pathways in glomerulonephritis

2020 ◽  
Vol 319 (4) ◽  
pp. F571-F578
Author(s):  
Maki Urushihara ◽  
Shuji Kondo ◽  
Yukiko Kinoshita ◽  
Natsuko Ozaki ◽  
Ariunbold Jamba ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Mesangial Cells ◽  
Macrophage Infiltration ◽  
Crescent Formation ◽  
Sirna Treatment ◽  
Extracellular Signal ◽  
Parietal Epithelial Cells

(Pro)renin receptor [(P)RR] has multiple functions, but its regulation and role in the pathogenesis in glomerulonephritis (GN) are poorly defined. The aims of the present study were to determine the effects of direct renin inhibition (DRI) and demonstrate the role of (P)RR on the progression of crescentic GN. The anti-glomerular basement membrane nephritis rat model developed progressive proteinuria (83.64 ± 10.49 mg/day) and glomerular crescent formation (percent glomerular crescent: 62.1 ± 2.3%) accompanied by increased macrophage infiltration and glomerular expression of monocyte chemoattractant protein (MCP)-1, (P)RR, phospho-extracellular signal-regulated kinase (ERK)1/2, Wnt4, and active β-catenin. Treatment with DRI ameliorated proteinuria (20.33 ± 5.88 mg/day) and markedly reduced glomerular crescent formation (20.9 ± 2.6%), induction of macrophage infiltration, (P)RR, phospho-ERK1/2, Wnt4, and active β-catenin. Furthermore, primary cultured parietal epithelial cells stimulated by recombinant prorenin showed significant increases in cell proliferation. Notably, while the ERK1/2 inhibitor PD98059 or (P)RR-specific siRNA treatment abolished the elevation in cell proliferation, DRI treatment did not abrogate this elevation. Moreover, cultured mesangial cells showed an increase in prorenin-induced MCP-1 expression. Interestingly, (P)RR or Wnt4-specific siRNA treatment or the β-catenin antagonist XAV939 inhibited the elevation of MCP-1 expression, whereas DRI did not. These results suggest that (P)RR regulates glomerular crescent formation via the ERK1/2 signaling and Wnt/β-catenin pathways during the course of anti-glomerular basement membrane nephritis and that DRI mitigates the progression of crescentic GN through the reduction of (P)RR expression but not inhibition of prorenin binding to (P)RR.

scholarly journals Membranous nephropathy followed by anti-glomerular basement disease: A case report and review of clinical presentation and treatment

2018 ◽  
Vol 6 ◽  
pp. 2050313X1880762
Author(s):  
Claudius Speer ◽  
Matthias Martin Gaida ◽  
Rüdiger Waldherr ◽  
Christian Nusshag ◽  
Florian Kälble ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Glomerular Basement Membrane ◽  
Membranous Nephropathy ◽  
Clinical Presentation ◽  
Rapidly Progressive Glomerulonephritis ◽  
Renal Vein Thrombosis ◽  
Simultaneous Occurrence ◽  
Rapid Decline ◽  
Crescent Formation ◽  
Vein Thrombosis

Membranous nephropathy is a common cause of nephrotic syndrome in adults and can be primary or secondary through autoimmune disease, medication, infection, or malignancy. Rapidly progressive glomerulonephritis with crescent formation is rare in patients with membranous nephropathy. Thus, in cases with rapid decline in renal function, after excluding complications such as malignant hypertension, acute hypersensitivity interstitial nephritis, and bilateral renal vein thrombosis, the simultaneous occurrence of a superimposed glomerulonephritis should be considered. We report a 55-year-old man suffering from a biopsy-confirmed primary membranous nephropathy, who developed rapidly progressive glomerulonephritis with anti-glomerular basement membrane antibodies after being affected with membranous nephropathy for 8 years. The kidney biopsy revealed a concurrence of membranous nephropathy and anti-glomerular basement membrane disease. Clinical presentation and treatment of membranous nephropathy followed by anti-glomerular basement membrane disease are discussed based on our observation with promising follow-up.

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