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Biomedical subjects

W G Couser

Publications and source records attributed to W G Couser.

At least 91 records · Page 5Linked to original sources
PubMed1993

Membranoproliferative glomerulonephritis associated with hepatitis C virus infection.

BACKGROUND AND METHODS: Hepatitis C virus (HCV) infection causes both acute and chronic liver disease and is also associated with mixed cryoglobulinemia. Whether HCV is also associated with renal disease, as is the hepatitis B virus, is not known. We describe the clinical, pathologic, virologic, and immunologic features of eight patients with HCV infection who were referred to nephrologists for glomerulonephritis. Four patients were treated with interferon alfa. RESULTS: All eight patients had proteinuria, and seven had decreased renal function. Renal biopsy in all patients revealed membranoproliferative glomerulonephritis, characterized by the deposition of IgG, IgM, and C3 in glomeruli. Electron microscopy of the biopsy specimens showed cryoglobulin-like structures in three of four patients. All eight patients had HCV RNA detected in their serum, elevated serum aminotransferase concentrations, and hypocomplementemia, and the majority had cryoglobulins and circulating immune complexes in their serum. Cryoprecipitates from the three patients who were tested contained HCV RNA and IgG anti-HCV antibodies to the nucleocapsid core antigen (HCVc or c22-3). IgM rheumatoid factors, present in all patients, bound anti-HCV IgG in all six patients tested. Four patients received interferon alfa for 2 to 12 months; all had evidence of decreased HCV replication and improvement of their renal and liver disease. CONCLUSIONS: Chronic HCV infection is associated with cryoglobulinemia and membranoproliferative glomerulonephritis. The pathogenesis is unknown, but may relate to deposition within glomeruli of immune complexes containing HCV, anti-HCV IgG, and IgM rheumatoid factors.

Adult↗
PubMed1993

Mediation of immune glomerular injury.

Although glomerular disease remains the most common cause of end-stage renal disease worldwide, major advances have been made recently in understanding the cellular and molecular mechanisms which mediate these disorders. Nephrotic syndrome in non inflammatory lesions such as minimal-change/focal sclerosis and MN results from disorders of the GEC which can be simulated in animal models by antibodies to various GEC membrane epitopes. Clarification of how these antibodies effect the GEC to induce a loss of glomerular barrier function should substantially improve understanding of the pathogenesis of minimal change/focal sclerosis. In MN, proteinuria is mediated primarily by C5b-9 through similar mechanisms that also involve the GEC as a target. Inflammatory glomerular lesions are induced by circulating inflammatory cells or proliferating resident glomerular cells. Understanding of how these cells induce tissue injury has also evolved considerably over the past decade. Neutrophil-induced disease involves leukocyte adhesion molecules in regulating neutrophil localization; proteases, oxidants, and myeloperoxidase in mediating injury and platelets in augmenting these processes. The activated mesangial cell exhibits altered phenotype and proliferation with release of oxidants and proteases. Mesangial cell proliferation may be initiated by basic fibroblast growth factor and is maintained by an autocrine mechanism involving PDGF. TGF-beta is important in the subsequent development of sclerosis. As understanding of these areas evolves, numerous new therapeutic strategies can now be devised, including agents which block or inhibit complement effects, oxidants, proteases, growth factors, and other cytokines. Appreciation of the role of several natural inhibitors of these mechanisms may also allow therapeutic manipulations that upregulate regulatory proteins, with a consequent therapeutic benefit.(ABSTRACT TRUNCATED AT 250 WORDS)

Glomerulonephritis, Membranous↗
PubMed1993

Defective lipolysis persists in hearts of rats with heymann nephritis in the absence of nephrotic plasma.

Catabolism of triglyceride-rich lipoproteins, including chylomicrons (CM), is reduced in the nephrotic syndrome. It has been suggested that hyperlipidemia per se might lead to reduced CM catabolism by saturating catabolic sites. Evidence also implicates disordered high-density lipoprotein function as reducing the activity of lipoprotein lipase (LPL), the final effector of CM lipolysis. To establish whether CM lipolysis would be abnormal in the absence of either abnormal rat lipoproteins or hyperlipidemia, we measured CM lipolysis by isolated perfused hearts of rats with passive Heymann nephritis. We found that lipolysis was significantly reduced by 30% at 30 minutes (246 +/- 40 mumol v 164 +/- 10 mumol fatty acid released/hr, P < 0.05). Uptake of fatty acids was also significantly less in nephrotic hearts than in control hearts (7.25% +/- 0.93% of dose v 3.32% +/- 0.011% of dose, P < 0.01). Total heart LPL activity was reduced by 40% in hearts of nephrotic animals (368.5 +/- 39.4 mumol v 210.6 +/- 25.9 mumol free fatty acid released/hr/g heart, P < 0.01). The heparin-releasable LPL pool is that pool bound to the vascular endothelium and represents the biologically active fraction. We perfused hearts with heparin and found that heparin-releasable LPL was reduced by an order of magnitude in hearts from nephrotic rats (173 +/- 33 mumol v 19.4 +/- 11.7 mumol free fatty acid released/hr/heart, P < 0.001). The decrease in this pool represented nearly entirely the difference in total heart LPL in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Heparin suppresses mesangial cell proliferation and matrix expansion in experimental mesangioproliferative glomerulonephritis.

Proliferation and extracellular matrix (ECM) overproduction by glomerular mesangial cells characterizes many types of glomerulonephritis and often precedes the development of glomerulosclerosis. Heparin is a potent inhibitor of mesangial cell growth in vitro. We examined whether standard heparin can inhibit mesangial cell proliferation in vivo in the mesangioproliferative anti-Thy 1.1 nephritis. Untreated control rats were compared to rats infused with heparin either early (day -2 to 1) or late (day 2 to 5) after induction of anti-Thy 1.1 nephritis. The results show that heparin treatment significantly reduced mesangial cell proliferation regardless of when it was initiated. Heparin (either early or late treatment) also reduced mesangial basic fibroblast growth factor (bFGF) expression and platelet-derived growth factor (PDGF) receptor up-regulation as reflected by immunostaining, whereas PDGF B-chain expression was reduced only by late heparin treatment. Furthermore, heparin treatment markedly inhibited the mesangial matrix expansion for a variety of ECM proteins, including laminin, type I and IV collagen, fibronectin and entactin. Heparin did not affect the initial mesangiolysis, glomerular macrophage influx, deposition of anti-Thy 1.1 IgG or fibrinogen, or the glomerular platelet influx. These results suggest that heparin, via its antiproliferative rather than anticoagulant effect, can inhibit mesangial cell proliferation, overexpression of polypeptide growth factors, and ECM protein overproduction in vivo. The beneficial effect of heparin can be demonstrated even if treatment is initiated after the development of nephritis. By virtue of these properties, heparin may be an effective agent in the treatment of human mesangioproliferative disease and in the prevention of glomerulosclerosis.

Animals↗
PubMed1993

Role of platelet-derived growth factor in glomerular disease.

An approach for establishing a role for a growth factor in glomerular disease is presented. Using platelet-derived growth factor (PDGF) as an example, there is strong evidence to support the hypothesis that PDGF is a mediator of mesangial cell proliferation in glomerulonephritis. This includes evidence that (1) PDGF is a mitogen for mesangial cells in culture; (2) PDGF is expressed in both experimental and human glomerulonephritis in which mesangial cell proliferation occurs; (3) infusion of PDGF into rats induces mesangial cell proliferation and a hypercellular lesion; and (4) inhibition of PDGF in a model of experimental nephritis significantly reduces the mesangial cell proliferation. However, these data do not answer the question of whether or not the inhibition of PDGF in human diseases would be beneficial in the long term, because some cell proliferation is likely required for normal healing and repair. Further studies will be necessary to resolve this issue.

Animals↗
PubMed1993

Glomerular C3c localization indicates ongoing immune deposit formation and complement activation in experimental glomerulonephritis.

In antibody-mediated glomerular disease, deposits of C3 (C3b) are common and are degraded by factor I to C3c and C3d. However, the kinetics of C3b degradation in glomerulonephritis have not been defined. To do this, we studied three models of complement-dependent glomerulonephritis with established C3 deposits (passive Heymann nephritis, cationized immunoglobulin G membranous nephropathy, and concanavalin A-anticoncanavalin A glomerulonephritis). C3b deposition was halted by administration of cobra venom factor, and the disappearance of C3c and C3d from glomeruli was measured with specific antibodies and quantitative fluorescence densitometry. Results showed that C3c deposits were reduced by over 85% within 24 hours in all three models. C3c clearance was unaffected by site or mechanism of deposit formation. C3d deposits persisted despite lack of ongoing complement activation. In passive Heymann nephritis when disease activity was monitored by urinary C5b-9 excretion, C3c was cleared in parallel with return of urine C5b-9 excretion to normal values. We conclude that glomerular deposits of C3c are cleared within 24 hours of cessation of complement activation. Positive staining for C3 utilizing antibody specific for the C3c portion documents recent complement activation usually reflecting new immune deposit formation.

Animals↗
PubMed1993

Pathogenesis of glomerulonephritis.

This review summarizes current understanding of the mechanisms which mediate immune glomerular injury in glomerulonephritis. Non-inflammatory lesions resembling minimal change disease and membranous nephropathy, respectively, are induced by non-complement fixing antibodies to glomerular epithelial cell (GEC) membrane antigens (minimal change disease) and GEC membrane insertion of the C5b-9 membrane attack complex of complement (membranous nephropathy). The cellular mechanisms of these effects are unclear but may involve GEC activation and release of local mediators, such as proteases or oxidants, or GEC detachment from underlying basement membrane. Inflammatory types of glomerular lesions are mediated by circulating inflammatory cells (neutrophils, platelets, macrophages) or by resident glomerular cells (mesangial cells) or both. Neutrophil-mediated injury involves local release of GBM degrading proteases or GBM halogenation induced by the interaction of neutrophil-derived myeloperoxidase with H2O2 and a halide. Neutrophil induced glomerular injury is augmented by platelets. Recent evidence establishes that mesangial cell proliferation in glomerulonephritis is mediated by complement and platelets. Mesangial cell proliferation is accompanied by increased expression of PDGF and PDGF receptor proteins and the genes for these proteins resulting in an autocrine mechanism of cell proliferation. Mesangial cell proliferation is also accompanied by increased release of neutral proteinase in sites of basement membrane damage. Mesangial cell proliferation precedes up-regulation of genes for extracellular matrix components in several models and may be important in the pathogenesis of glomerulosclerosis.

Animals↗
PubMed1993

Visceral glomerular epithelial cells can proliferate in vivo and synthesize platelet-derived growth factor B-chain.

In glomerular diseases associated with antibody- and complement-mediated injury to endothelial and mesangial cells, cell proliferation is an important early response that precedes matrix accumulation and glomerulosclerosis. In contrast, in diseases in which the visceral glomerular epithelial cell (vGEC) is the principal target of injury, cell proliferation is not a recognized consequence, although vGECs respond in vitro to a variety of growth factors and inflammatory mediators. To explore the possibility that low levels of vGEC proliferation may occur and participate in such diseases, serial studies were done in the passive Heymann nephritis model of membranous nephropathy, in which the vGEC is the primary target of antibody- and C5b-9-mediated injury. The results showed mitotic figures and positive staining for the proliferating cell nuclear antigen in cells whose location defined them as vGECs. The proliferating cell nuclear antigen-positive cells at the edge of the capillary wall were confirmed to be vGECs by double-immunostaining with antibodies to SPARC/osteonectin, which preferentially label vGECs in passive Heymann nephritis. Proliferation of vGECs in vivo was preceded by increased glomerular expression of platelet-derived growth factor (PDGF) B-chain protein and messenger RNA, both of which localized to vGECs. PDGF B-chain protein and messenger RNA were also detected in cultured vGECs. PDGF receptor beta-subunit protein or messenger RNA could not be demonstrated in vGECs in vivo or in vitro, and no growth response of cultured vGECs to PDGF was noted. These results suggest that proliferation of vGECs does occur in a model of glomerular injury induced by antibody and C5b-9 on vGECs. VGEC proliferation and production of PDGF may be involved in the restoration of the capillary wall but could also contribute to local capillary wall injury and proliferation of other cells in Bowman's capsule, interstitium, and tubules.

Animals↗
PubMed1992

Mesangial cells in the pathogenesis of progressive glomerular disease in animal models.

Increasing evidence supports a role for glomerular mesangial cell proliferation and over-production of extracellular matrix by mesangial cells in the development of focal or diffuse glomerulosclerosis. Experimental data obtained mainly in the chronic progressive remnant kidney model and in the acute mesangioproliferative anti-Thy 1.1 glomerulonephritis in rats have shed some insights into the factors governing mesangial cell proliferation and matrix synthesis in vivo. In these experimental models, mesangial cell activation can be demonstrated early in the course of disease as exemplified by the de novo expression by the mesangial cell of a smooth muscle "specific" actin isotype (i.e., alpha-smooth muscle actin). Following mesangial cell activation, cellular proliferation ensues both in the acute anti-Thy 1.1 model and, to a lesser degree, in the chronic remnant kidney model. While a multitude of mitogens for mesangial cells has been proposed on the basis of in vitro experiments, the factors involved in the regulation of mesangial cell proliferation in vivo remain largely undefined. Three growth factors which may have important roles in the in vivo mesangioproliferative response are platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and transforming growth factor-beta (TGF-beta). All three cytokine growth factors are present in various inflammatory cells as well as in mesangial cells themselves, thereby allowing these factors to mediate cell proliferation by either paracrine and/or autocrine pathways. In vivo studies show that PDGF, bFGF, and TGF-beta participate in the mesangial cell proliferation and/or the mesangial matrix expansion that follows mesangial cell injury with anti-Thy 1.1 antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Altered glomerular extracellular matrix synthesis in experimental membranous nephropathy.

Chronic progressive membranous nephropathy (MN) in humans is characterized by thickening of the glomerular basement membrane (GBM) with formation of spikes which contain laminin and other extracellular matrix (ECM) proteins. We have utilized two models of MN in the rat (active and passive Heymann nephritis, AICN, PHN) to define the sequential changes in composition of GBM as they relate to changes in glomerular gene expression for ECM components, altered permeability and morphological changes. Renal biopsies obtained during the course of AICN and PHN were immunostained for various ECM proteins and total glomerular RNA was hybridized with cDNA probes specific for laminin B2-chain, s-laminin, and types I and IV collagen. In addition, the ability of anti-glomerular epithelial cell (GEC) antibody and complement on rat GEC in culture to induce laminin release or laminin and s-laminin mRNA expression was determined. The results demonstrate that at weeks 12, 16, and 20 of AICN, immunostaining for laminin, s-laminin, fibronectin, entactin, and heparan sulfate proteoglycan increased in the GBM in a spike-like pattern. Concomitantly, glomerular mRNA levels of laminin B2-chain and of s-laminin increased. Type IV collagen protein and gene expression remained unchanged or decreased. No glomerular immunostaining for type I collagen occurred during AICN despite increased expression of mRNA for this collagen type. In contrast to AICN, in PHN no pronounced changes of the glomerular ECM occurred, except for transient expression of type I collagen mRNA in whole glomerular RNA and type I collagen protein the GEC cytoplasm. Stimulation of GEC in culture with anti-GEC antibody and complement also failed to induce transcription of laminin or s-laminin mRNA or the release of laminin protein. These findings suggest that the polyantigenic expansion of GBM which occurs in chronic experimental MN may be stimulated by factors different from the C5b-9 mediated processes that cause the initial proteinuria.

Animals↗
PubMed1992

Glomerular cell proliferation and PDGF expression precede glomerulosclerosis in the remnant kidney model.

Increasing evidence supports a role of glomerular cell proliferation in the development of focal or diffuse glomerulosclerosis. This study investigates the chronology and sequence of cellular events that precede glomerulosclerosis in 5/6 nephrectomized rats. Within three days of renal ablation, a phenotypic switch occurred in which some mesangial cells expressed alpha-smooth muscle actin. This was followed by proliferation of mesangial cells, and to a lesser degree endothelial cells from day 5 to week 4 as detected by immunostaining for the proliferating cell nuclear antigen (PCNA). Glomerular cell proliferation was accompanied by increased immunohistochemical expression of PDGF B-chain. In situ hybridization showed no glomerular PDGF B-chain mRNA expression at the induction of proliferation (day 5), and a marked increase between week 1 and 4 in operated rats. In parallel, increased expression of PDGF receptor beta-subunit protein and mRNA was demonstrated by immunohistochemistry and Northern analysis of total glomerular RNA. The onset of glomerular cell proliferation was also associated with mild glomerular platelet accumulation (as defined by 111In-labelled platelet studies) as well as with fibrinogen deposition. Proteinuria, glomerular sclerotic changes, and leukocyte infiltration all followed cell proliferation. The glomerular leukocyte infiltrate consisted of monocytes/macrophages and increased markedly at week 10 in rats with renal ablation. Thus, our results suggest that in the remnant kidney model: 1) proliferation of intrinsic glomerular cells precedes glomerulosclerosis; 2) proliferation may be initiated by degranulating platelets and sustained by PDGF released from intrinsic glomerular cells; and 3) glomerular monocyte/macrophage infiltration occurs after the proliferation, and may possibly contribute to the development of glomerular sclerotic changes.

Actins↗
PubMed1992

The activated mesangial cell: a glomerular "myofibroblast"?

The glomerular mesangial cell may have several important beneficial functions in the normal glomerulus. These include the production of growth factors to allow normal cell turnover, the provision of structural support for the capillaries via the production of mesangial matrix, and the modulation of glomerular hemodynamics via their contractile properties. However, in various types of glomerular injury, the mesangial cell may acquire characteristics of a "myofibroblast", which may in fact be injurious to the glomerulus. These "activated" mesangial cells can be shown to be proliferating by one or more mechanisms that are mediated by platelets and that also involve the local production of platelet-derived growth factor. Like myofibroblasts in other tissues, the mesangial cell acquires smooth muscle cell-like properties, characterized by the de novo expression of alpha-smooth muscle actin, and by the development of fibroblast-like properties, characterized by the production of interstitial collagens in addition to normal mesangial matrix constituents. Identifying therapeutic strategies that prevent this phenotypic modulation of the mesangial cell may provide new ways to treat golmerular diseases.

Animals↗
PubMed1992

Glomerular epithelial cells secrete a glomerular basement membrane-degrading metalloproteinase.

Cultured rat glomerular epithelial cells (GEC) were examined for their ability to release extracellular matrix-degrading proteinases with [3H]gelatin as substrate. GEC-conditioned media, under serum-free conditions, contained modest amounts of gelatinase activity (1 to 10 U/mg of protein); the activity was maximal at neutral pH, was inhibited by zinc chelators, was not inhibited by tissue inhibitor of metalloproteinase-2, and could not be further activated by trypsin or organomercurials. Gelatin substrate sodium dodecyl sulfate-polyacrylamide gels of GEC-conditioned medium revealed several zones of lysis, with molecular sizes of 150 kd (major band), and 220, 86 to 93, and 52 to 54 kd (minor bands). Northern blot analysis demonstrated that the GEC metalloproteinase(s) were distinct from the 68- to 72-kd type IV collagenase/gelatinase present in mesangial cells or the 92-kd type IV collagenase present in neutrophils. The GEC gelatinolytic activity also degraded insoluble type IV collagen in glomerular basement membrane in a dose-dependent manner. The major metalloproteinase activity responsible for the type IV collagen degradation has a molecular size of 150 kd with a type IV collagen substrate gel. Thus, GEC produce several neutral metalloproteinases, which, by virtue of their substrate specificity, may play an important role in glomerular basement membrane remodeling and in glomerular diseases characterized by alterations in basement membrane permeability.

Animals↗
PubMed1992

Markers of complement-dependent and complement-independent glomerular visceral epithelial cell injury in vivo. Expression of antiadhesive proteins and cytoskeletal changes.

BACKGROUND: Visceral glomerular epithelial cells (GEC) are an important component of the glomerular filtration barrier to proteins. While ultrastructural GEC changes have frequently been observed in proteinuric states, no suitable light microscopic markers of GEC injury have yet been identified. EXPERIMENTAL DESIGN: We have analyzed in vivo the GEC expression of proteins known to be involved in cell shape changes. SPARC (osteonectin, BM-40) and tenascin (cytotactin, J1, hexabrachion) belong to a group of anti-adhesive glycoproteins, that modulate cell-matrix interactions. We also studied cytoskeletal intermediate filament proteins, including desmin and vimentin. The GEC expression of SPARC, tenascin, desmin, and vimentin was analyzed in various types of GEC injury in the rat, including complement-mediated injury (passive Heymann nephritis, autologous immune complex nephritis, conA anti-conA nephritis), complement-independent injury (nephrotoxic nephritis), toxic injury (aminonucleoside nephrosis) and hypertensive injury (5/6 nephrectomy, angiotensin-II infusion). A complement-mediated model of mesangial cell injury (anti-Thy 1.1 mesangial proliferative nephritis) served as a control. RESULTS: SPARC mRNA and protein were constitutively expressed in normal rat glomeruli. Immunostaining and immunoelectron microscopy primarily localized SPARC to the cytoplasm of GEC. Markedly increased glomerular SPARC synthesis and GEC immunostaining was observed in all instances of complement-mediated GEC injury but in none of the other conditions. In contrast, glomerular immunostaining for tenascin, that also stained in a GEC pattern, either remained unchanged or increased to a minor degree (complement-mediated models). GEC immunostaining for desmin in normal rats was low and variable, and increased significantly in any form of GEC injury but not in anti-Thy 1.1 nephritis. No concomitant increase of GEC immunostaining for vimentin was detectable, which could have been due to the constitutively high expression of vimentin in GEC. CONCLUSIONS: SPARC and desmin, but not tenascin or vimentin, are suitable light microscopic markers of GEC injury. The combined staining for these proteins may be useful in differentiating the mechanisms of GEC injury.

Animals↗
PubMed1992

Structural characterization of the mesangial cell type IV collagenase and enhanced expression in a model of immune complex-mediated glomerulonephritis.

Secretion of glomerular cell-derived matrix metalloproteinases (MMPs) and their specific inhibitors, TIMP-1,2, may play an important role in the turnover of the glomerular extracellular matrix under basal and pathologic conditions. A 66-68 kd MMP secreted by cultured mesangial cells (MC) with activity against Type IV collagen and gelatin was purified and shown by amino-acid sequence analysis to be identical with a Type IV collagenase/gelatinase secreted by certain transformed tumor cell lines. The expression of the mesangial MMP in vivo was limited within the kidney to a small subset of the intrinsic glomerular mesangial cell population. After induction of acute anti-Thy 1.1 glomerulonephritis, there was a large increment in the number of Type IV collagenase-secreting MC, temporally coincident with the development of mesangial hypercellularity. The expression of the MMP inhibitor protein, TIMP-1, was not changed over this period. Ultrastructural studies localized the mesangial MMP to areas of evolving mesangiolysis and at sites of glomerular basement membrane disruption. Enhanced expression of the mesangial cell-derived Type IV collagenase may contribute to the evolution of glomerular injury in this model of immune complex-mediated glomerulonephritis or may be involved in the extensive matrix remodeling process that accompanies this form of glomerular injury.

Amino Acid Sequence↗
PubMed1992

Glomerular cells, extracellular matrix accumulation, and the development of glomerulosclerosis in the remnant kidney model.

Expansion of the mesangial extracellular matrix (ECM) with subsequent glomerular sclerosis is a prominent finding in most progressive renal diseases. To investigate the chronology of accumulation of ECM components as it relates to previously described cellular events, biopsies were obtained from rats at various times following 5/6-nephrectomy as well as from sham-operated controls. The biopsies were stained with PAS as well as immunostained for PCNA (a cell proliferation marker), monocytes/macrophages, types I and IV collagen, laminin, s-laminin, fibronectin, heparan sulfate proteoglycan and entactin/nidogen. Immunostaining of biopsies obtained from 5/6 nephrectomized rats demonstrated an early glomerular cell proliferation, peaking at week 2. Expansion of the glomerular tuft area with rare glomeruli demonstrating focal sclerosis were also seen at week 2. Glomerular macrophage influx correlated with later ECM expansion and glomerulosclerosis. A progressive accumulation of all ECM proteins investigated was noted in the pathological mesangial matrix at week 2 and later time points. Northern analysis of total glomerular RNA at weeks 2 and 6 after 5/6 nephrectomy showed de novo expression type I collagen mRNA as well as small increases of glomerular mRNA levels for type IV collagen (1.2- and 1.4-fold over control RNA) and laminin (1.3- and 1.5-fold) but not s-laminin (1.1- and 0.9-fold). We conclude that cellular events including glomerular cell proliferation and macrophage influx are associated with increased gene and protein expression by ECM proteins in the remnant kidney model and may contribute to the development of sclerosis.

Animals↗