Mesangial factor V expression colocalized with fibrin deposition in IgA nephropathy

Liu, Ning; Ono, Takahiko; Suyama, Katsuo; Nogaki, Fumiaki; Shirakawa, Kiichi; Maeda, Morihiro; Kawamura, Tsuneo; Kamata, Tadashi; Oyama, Atsushi; Muso, Eri; Sasayama, Shígetake

doi:10.1046/j.1523-1755.2000.00206.x

Cited by 33 publications

(40 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To discern the cellular expression of PMAT in the glomeruli, double immunofluorescence labeling was performed on human kidney cryosections using established cell type-specific markers for podocytes, mesangial cells, and glomerular endothelial cells-the three major cell types that make up the glomerulus. No overlap of specific PMAT staining was observed with ␣-smooth muscle actin (␣-SMA), a cell body marker for mesangial cells (13), or CD31, a cell surface marker for endothelial cells (24) (Fig. 3, A and B).…”

Section: Resultsmentioning

confidence: 99%

Podocyte-specific expression of organic cation transporter PMAT: implication in puromycin aminonucleoside nephrotoxicity

Li¹,

Zhou²,

Kalhorn³

et al. 2009

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

show abstract

Section: Resultsmentioning

confidence: 99%

Podocyte-specific expression of organic cation transporter PMAT: implication in puromycin aminonucleoside nephrotoxicity

Li¹,

Zhou²,

Kalhorn³

et al. 2009

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

show abstract

“…3,25 In our previous study, factor V mRNA expression was observed in mesangial cells of IgA nephropathy with activity. 2 Taken together, the activation of local coagulation in the mesangial area may progress in MsPGN. Hung H-L and High KA reported that liver contained the highest amounts of factor X mRNA; however, factor X was also detected in various organs, including the kidney, at trace level.…”

Section: Roles Of Factor Xa In Rat Mspgnmentioning

confidence: 98%

“…These fixed sections were stained by an indirect method using a goat anti-mouse tissue factor antibody (Santa Cruz Biotechnology, Santa Cruz, CA, USA), a sheep anti-human factor V antibody (Cedarlane Laboratories), a goat anti-human factor X antibody (Santa Cruz Biotechnology), or a goat anti-mouse PAR2 antibody (Santa Cruz Biotechnology), as described previously. 2 Sections were then incubated with appropriate secondary antibodies, and color was developed as mentioned above. The specificity of the anti-PAR2 antibody was previously reported by blocking test, using specific immunizing blocking peptide.…”

Section: Histological Evaluation Of Renal Tissuementioning

confidence: 99%

“…1 In a previous study, we showed that coagulation factor V is colocalized with fibrin in the mesangial area in an active type of IgA nephropathy with mesangial cell proliferation. 2 In another in vitro study, we observed that the coagulation process proceeds on the surface of cultured mesangial cells via the expression of factor V after the stimulation of an inflammatory cytokine TNF-a with exogenous factor Xa. 3 Furthermore, Monno et al 4 have shown that factor Xa directly promotes mesangial cell proliferation in vitro.…”

mentioning

confidence: 94%

See 1 more Smart Citation

Roles of coagulation pathway and factor Xa in rat mesangioproliferative glomerulonephritis

Nomura

Liu

Nagai

et al. 2007

Laboratory Investigation

Self Cite

View full text Add to dashboard Cite

Tissue factor initiates the extrinsic coagulation pathway by activating coagulation factor X to factor Xa, and factor V is a cofactor for the prothrombin activation by factor Xa. As factor Xa is known to promote the proliferation of mesangial cells in culture, the roles of the coagulation pathway and factor Xa were studied in an animal model of mesangioproliferative glomerulonephritis (MsPGN). MsPGN was induced in Wistar rats by an intravenous injection of anti-Thy 1.1 monoclonal antibody, OX-7. To clarify the role of factor Xa in MsPGN, a specific factor Xa inhibitor, DX-9065a, was injected intravenously at 2.5 or 10 mg/kg at the same time as OX-7, and kidney involvement was assessed by immunohistological analyses. We also examined p44/42 mitogen-activated protein (MAP) kinase activation. Time-course study revealed that expressions of tissue factor, factor V, and protease-activated receptor 2 (PAR2) were peaked on day 3, followed by factor X accumulation and mesangial proliferation. DX-9065a treatment significantly ameliorated proteinuria in a dose-dependent manner on day 8. Histological analyses showed a significant reduction in the size of glomeruli, the total number of glomerular cells, and crescent formation by DX-9065a treatment. Macrophage infiltration, which was rapidly observed on day 1 in disease control rats was not inhibited on days 1-3 by DX-9065a treatment, however it was suppressed on days 5-8. The deposition of fibrin, the number of PCNA-positive cells, and phosphorylation of p44/42 MAP kinase were markedly increased in the disease control group, whereas they were significantly reduced in the treatment group. Tissue factor and factor V induction may accelerate MsPGN through the activation and accumulation of factor X via proinflammatory and procoagulant mechanisms, and the inhibition of factor Xa would be a promising method to regulate the disease process.

show abstract

“…2,3) Also in human and experimental diabetic nephropathy, glomerular fibrin deposition and extracellular matrix (ECM) expansion have been noted. 4,5) In this context, transforming growth factor b (TGF-b) is upregulated in kidney diseases, and TGF-b promotes the production of various ECM proteins.…”

mentioning

confidence: 99%

Roles of Coagulation Pathway and Factor Xa in the Progression of Diabetic Nephropathy in db/db Mice

Sumi

Yamanaka-Hanada

Bai

et al. 2011

Biological & Pharmaceutical Bulletin

Self Cite

View full text Add to dashboard Cite

The active type of coagulation factor X (factor Xa) activates various cell-types through protease-activated receptor 2 (PAR2). We previously reported that a factor Xa inhibitor could suppress Thy-1 nephritis. Considering that fibrin deposition is observed in diabetic nephropathy as well as in glomerulonephritis, this study examined the roles of the coagulation pathway and factor Xa in the development of diabetic nephropathy using type 2 diabetic model mice. Diabetic (db/db) and normoglycemic (m؉/m؉) mice were immunohistochemically evaluated for their expression/deposition of PAR2, transforming growth factor (TGF)-b b, fibrin, extracellular matrix (ECM) proteins, and CD31 at week 20. Significantly greater numbers of PAR2-positive cells and larger amounts of fibronectin, and collagen IV depositions were observed in the glomeruli of db/db mice than those in m؉/m؉ mice. Next, expression of PAR2 versus deposition of collagen IV and fibronectin was compared between week 20 and week 30, and the number of PAR2-positive cells in the glomeruli decreased in contrast with the increased accumulation of ECM proteins. In an intervention study, fondaparinux, a factor Xa inhibitor, was subcutaneously administered for ten weeks from week 10 to 20. Fondaparinux treatment significantly suppressed urinary protein, glomerular hypertrophy, fibrin deposition, expression of connective tissue growth factor, and ECM proteins deposition together with CD31-positive capillaries. These results suggest that coagulation pathway and glomerular PAR2 expression are upregulated in the early phase of diabetes, together with the increase of profibrotic cytokines expression, ECM proteins deposition and CD-31-positive vessels. Factor Xa inhibition may ameliorate glomerular neoangiogenesis and ECM accumulation in diabetic nephropathy.

show abstract

Mesangial factor V expression colocalized with fibrin deposition in IgA nephropathy

Abstract: The present findings suggest that factor V is strongly expressed in mesangial cells in active IgAN accompanied with mesangial proliferation and may exert procoagulant activity, leading to intramesangial coagulation.

Cited by 33 publications

References 31 publications

Podocyte-specific expression of organic cation transporter PMAT: implication in puromycin aminonucleoside nephrotoxicity

Podocyte-specific expression of organic cation transporter PMAT: implication in puromycin aminonucleoside nephrotoxicity

Roles of coagulation pathway and factor Xa in rat mesangioproliferative glomerulonephritis

Roles of Coagulation Pathway and Factor Xa in the Progression of Diabetic Nephropathy in db/db Mice

Contact Info

Product

Resources

About