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At least 19 recordsLinked to original sources
PubMed1992

The glomerular mesangium: capillary support function and its failure under experimental conditions.

We present a structural analysis of the ability of the biomechanical unit consisting of mesangium and glomerular basement membrane to maintain normal capillary architecture in the face of mechanical challenges due to high intraglomerular pressures. Capillary support function may be considered in terms of the stabilization of local form (development of wall tension against capillary dilation) and global form (centripetal fixation of capillary loops to maintain higher order form). The pathologic consequences of the loss of this support are illustrated by way of experimental models of mechanical mesangial failure. Such failure may express itself as mesangial widening, increased transmesangial macromolecule "traffic," ballooning of capillary segments, and unfolding of capillary loops. Mechanisms are described by which these structural changes may lead to segmental glomerular sclerosis.

Animals↗
PubMed1985

Glomerular mesangium: its function and relationship to angiotensin II.

The glomerular mesangium is composed of mesangial cells and an intercellular material, the mesangial matrix. Partly because of its unique anatomic location, the mesangium appears to be susceptible to immune- and non-immune-mediated injury. Mesangial cells have characteristics similar to smooth muscle cells, and their surface is covered with receptors that bind a variety of vasoactive substances. The glomerular mesangium seems to play an important role in the physiologic regulation of the glomerular microcirculation. There is evidence that a plasmic flow carrying macromolecules circulates through the mesangium. Changes in glomerular hemodynamic determinants and in the release and/or production of vasoactive substances, particularly angiotensin II, can greatly influence the mesangial movement of macromolecules. Quantitative and/or qualitative alterations in the mesangial movement of macromolecules may lead to mesangial injury.

Angiotensin II↗
PubMed1988

Development of the glomerular mesangium.

The development of the glomerular mesangium was studied in fetal and newborn rat kidneys by using a widefield electron microscope which can cover a whole glomerulus within one low-power viewfield. A three-dimensional observation of the immature glomeruli was done by performing ultrathin serial sectionings of the specimen for electron microscopy. Scanning electron microscopic observation of the developing glomeruli was also performed. The developmental distribution of contractile protein (actin) in mesangial cells and the main intrinsic component of the extracellular matrix protein (type IV collagen) of the mesangium were examined by immunohistological techniques. The widefield electron micrograph revealed a precise relationship between the mesangium and other components of the glomerulus. The results confirmed that the capillary extends into the S-shaped body from the surrounding vascular system at the initiation of nephronogenesis. The mesangial cells are always continuous to the vascular pericyte-smooth muscle cell system during the whole course of glomerular development and they participate in the subdivision of the capillary network during glomerulogenesis. Morphological findings and the changing distribution of intra- and extracellular proteins of the mesangium during development suggest that the mesangial cell differentiates from the primitive pericyte of the immature capillary.

Actins↗
PubMed1993

The glomerular mesangium in diabetes mellitus.

Like the renal glomerular mesangium in patients with diabetic nephropathy, glomerular mesangial cell cultures grown in 30 mM glucose accumulate increased amounts of the extracellular matrix (ECM) proteins fibronectin, laminin, and type IV collagen. This is due to increased ECM protein synthesis and mRNA levels. Similar to other cells types that are affected by the diabetic state (such as, vascular cells and peripheral nerve), mesangial cells transport glucose by an insulin-independent, facilitated diffusion transport system. Kinetic studies reveal that intracellular glucose levels may reach the ambient glucose concentrations achieved in diabetes. Growth studies reveal that glucose does not exert its effect on mesangial cell ECM accumulation by affecting cell growth, but rather it causes an increase in diacylglycerol (DAG) mass and activates protein kinase C. Agents such as phorbol myristate acetate (PMA) and the cell permeable DAG analogue, oleoyl acetyl glycerol (OAG) which activate protein kinase C also increase ECM mRNAs. These results implicate protein kinase C activation in the increased ECM accumulation observed in mesangial cell cultures grown in high glucose.

Animals↗
PubMed1983

Neutral proteinase activity produced in vitro by cells of the glomerular mesangium.

Cells derived from isolated glomerular tufts of rats were studied in primary tissue culture after the removal of epithelial cells by collagenase treatment. The cultured cells, fusiform or stellate in shape, grew readily over a 12-day period. Immunofluorescence staining was positive for myosin and fibronectin, while negative for Factor VIII, suggesting that the outgrowing cells were derived from the glomerular mesangium. In serum-free culture, these cells produced neutral proteinase activity that occurred as a latent trypsin-activable form (apparent molecular weight range, 78,000 to 100,000 daltons) and in an active form (44,000 to 58,000 daltons). Neutral proteinase activity was inhibited by EDTA and by cysteine, and exhibited a pH optimum of 7.2 to 7.8, characteristic of an extracellularly active metalloendopeptidase. The culture supernate which contained the neutral proteinase activity was capable of degrading purified rat glomerular basement membrane. The release of hydroxyproline-containing fragments from the basement membrane indicated that degradation of the type IV collagen component of the basement membrane was occurring. These findings suggest that the neutral proteinase activity generated by mesangium-derived cells may play a role in the physiologic turnover of glomerular structural proteins in vivo.

Animals↗
PubMed1973

The glomerular mesangium. 3. Acute immune mesangial injury: a new model of glomerulonephritis.

A mechanism of immune glomerular injury is described based on the fixation of antibody (Ab) to an antigen (Ag) that has localized in the glomerular mesangium. Rabbits were given, intravenously (i.v.), aggregated human IgG (AHIgG) or albumin (AHSA) and 10 h later, when the Ag by immunofluorescent microscopy was present in the mesangium, a kidney was removed and transplanted into a normal rabbit. The recipient then received, i.v., rabbit anti-HIgG or anti-HSA. Within minutes of Ab infusion, glomeruli of the donor kidney had polymorphonuclear (PMN) infiltration that over the next few hours became marked and was associated with glomerular cell swelling. At 24 h a decrease in PMN's and early mesangial proliferation was seen. By 3 days there was marked mesangial hypercellularity and increased mesangial matrix. Within minutes after Ab administration rabbit IgG, C3, and fibrin were seen in the glomerular mesangium. There was a fall in complement titer by 1 min after Ab infusion that was due to complement consumption by the donor kidney. Complement then returned to normal levels by 48 h. Significant glomerular injury did not occur (a) in the recipient's own kidney, (b) from Ag administration and transplantation without recipient Ab administration, or (c) from transplantation and Ab administration without prior Ag administration. These studies demonstrated that Ag localized in the glomerular mesangium can react with circulating Ab and complement resulting in severe glomerular injury.

Animals↗
PubMed1994

[A study on the proliferative and sclerosing mechanism of glomerular mesangium].

The role of glomerular mesangial cells (MC) and mesangial matrix (MM) in glomerular sclerosis was studied by using rat mesangial cell culture, immunohistochemical studies for laminin, laminin receptors as well as collagen types IV and III. The effect of tumor necrosis factor (TNF) and endothelin (ET) on MC was also studied. Results show that TNF and ET have potent mitogenic effects on MC. The glomerular MC possess the special capability of secreting TNF and ET. TNF and ET can also influence and induce the secretion of each other. The MM is increased in the MC nodular colonies formed after prolonged culture. These colonies are composed of collagen IV and collagen III. Therefore, injuring factors can cause MC and MM to proliferate and produce glomerulosclerosis.

Animals↗
PubMed1980

Fibronectin as a marker for the glomerular mesangium in immunohistology of kidney biopsies.

Antibodies against fibronectin have been used as a marker for the glomerular mesangium in routine immunofluorescence microscopy of renal biopsies. Rhodamine-conjugated antibodies against fibronectin were used in this study of 22 human kidney biopsies and four histologically normal kidneys in combination with routinely employed fluorescein-conjugated antibodies against immunoglobulins, complement components, and fibrin. The distribution of fibronectin was similar to mesangial material demonstrable by silver impregnation. By the double staining procedure localization of deposits in relation to the mesangium was considerably facilitated. Variations in the mesangial fibronectin were observed; staining was increased in seven of 11 cases of mesangial glomerulonephritis, and decreased or absent in four of four cases of membranous glomerulonephritis and three of three cases of amyloidosis. Abnormal localization of fibronectin was observed in glomerular crescents and in the intertubular area together with fibrin in kidney transplants. The results suggest that antibodies against fibronectin are useful markers for the glomerular mesangium and that alterations in mesangial fibronectin may reflect the functi-nal state of the glomerulus. Abnormal localization in extramesangial areas may result from local synthesis or increased adsorption of circulating fibronectin to fibrin or collagen.

Adult↗
PubMed1997

Adhesion molecules in the glomerular mesangium.

Experimental evidence indicates that extensive "cross-talk" exists between glomerular cells, extracellular matrix molecules and soluble mediator substances affecting the proliferative and secretory phenotype of glomerular mesangial cells. Both matrix and cytokines regulate mesangial cell behavior in vitro and in vivo after binding to specific cell surface receptors. It appears as if the concerted action of insoluble and soluble ligands on mesangial cells involves a reciprocal regulation of matrix molecules and cytokines as well as expression and affinity of their respective receptors. Elucidation of the potential biologic and clinical relevance of cell-matrix interactions in the glomerular mesangium represents a challenging goal in current kidney research. This brief review summarizes recent investigations concerning regulation of expression and function of adhesion molecules and matrix receptors in the mesangium. In addition to results from cell culture studies, descriptive findings on expression and regulation of adhesion molecules and their potential role for altered mesangial cell behavior in glomerular disease is considered.

Animals↗
PubMed1989

High affinity binding sites for Perindopril a new inhibitor of angiotensin-I-converting enzyme (ACE) in the rabbit kidney: possible evidence for localization of ACE in endothelial structures and in glomerular mesangium.

The tissue distribution of Perindopril, a new potent inhibitor of the angiotensin-converting enzyme (ACE), was studied after in vivo intravenous injection into rabbits of tracer amounts of the tritiated drug either alone (no modification of the renin angiotensin system) or along with a pharmacologic dose of 10 mg/kg unlabelled Perindopril. Lung and kidneys were the most densely labelled tissues. Kidney distribution of tritiated Perindopril was studied either by histo-autoradiography or by measurement of radioactivity in the homogenates of dissected kidney zones. A close parallelism was found between the distribution patterns of ACE and radioactivity throughout the kidney. Tritiated-Perindopril binding was inhibited by concurrent treatment of the animals with the unlabelled drug or pretreatment with Captopril. Autoradiographic study of kidney slices after the administration of tracer amounts of Perindopril showed an intense labelling of the glomerular mesangium and of endothelial structures of blood vessels, and a lack of labelling of tubular epithelial cells. The possible occurrence of two pools of "ACE-like" activity in the kidney is discussed, namely i) one pool which is labelled by tritiated Perindopril, located in glomerular mesangium and endothelial structures which may be involved in the pharmacological action of ACE inhibitors; and ii) a second pool located in the proximal-tubule cell brush-border, remaining unlabelled by Perindopril, for which the high amount of neutral endopeptidase present at this site may be responsible.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1983

Contractile properties of the glomerular mesangium.

Mesangial cells together with the surrounding matrix material form the glomerular mesangium. These cells exhibit bundles of microfilaments in situ similar to smooth muscle cells and thus have been hypothesized to regulate glomerular perfusion and filtration by contracting. In this report I shall review data suggesting that the inherent glomerular mesangial cell responds to vasoactive stimuli by contracting to regulate glomerular function.

Angiotensin II↗
PubMed1995

The glomerular mesangium: studies of its developmental origin and markers in vivo and in vitro.

Cultured mesangial cells are widely used to explore their role in kidney glomerular functions, but methods to reliably identify these cells in vivo and in vitro are lacking. Furthermore, the proposed relationship of mesangial cells to e.g. fibroblasts and smooth muscle cells has not been systematically studied. Here we wanted to search for markers of practical use also in identifying cultured mesangial cells, and to apply these markers in a study of the origin of glomerular mesangium. No epitopes specific for only mesangial cells could be identified, and no evidence of their true relationship with neural or lymphocytic lineages could be found. Findings with the variety of markers used suggest that mesangial cells may be indistinguishable from smooth muscle cells and fibroblasts. A panel of antibodies, including those against Thy1.1, smooth muscle actin, desmin, cellular fibronectin and beta 1 integrin alpha 1 and alpha 5 chains, and Wistaria floribunda (WFA) and Ricinus communis (RCA I) lectins, were found useful for mesangial cell detection in vivo and in vitro. The origin of glomerular mesangial cells could not be conclusively determined, although the results indirectly suggest that mesangial cells together with endothelial cells migrate to the glomerulus from the outside.

Animals↗
PubMed1975

Antibodies reacting with the glomerular mesangium. Isolation and immunopathology.

Antigens of porcine lung were prepared by homogenization and ultrasonic treatment of lung tissue. The antigens were digested by collagenase and trypsin and chromatographed on Sephadex G 200. After immunization of rabbits with certain fractions of the chromatographed material, antibodies could be obtained in rabbits which fixed in vitro and in vivo in the glomerular mesangium of rats, hogs and the human, but not in the basement membrane of glomeruli of these species. Following intravenous injection into rats, the antibodies could be observed in the mesangial area without an apparent loss of antigenicity for 55 days. While 5 days after the application of 20 mg of the anti-mesangial IgG-preparation, there were no glomerular changes histologically demonstrable, after 55 days small amounts of rat-IgG could be demonstrated histochemically within the mesangium. Deposits of rat-complement (C3) could not be demonstrated with certainty. Severe morphological lesions were absent. Rats injected with the same doses of antibody and simultaneously immunized with rabbit-IgG showed a substantially greater deposit of autologous rat-IgG and rat-complement within the mesangial area after 55 days. By histological examination focal and segmental scleroses of the mesangium were determined. A significant pathological proteinuria did not occur. The present model constitutes a new possibility for studying the function of the glomerular mesangium.

Animals↗
PubMed1990

Structure of the glomerular mesangium: a biomechanical interpretation.

This paper summarizes our current knowledge of the structural details and probable functional significance of the system of contractile filaments in the glomerular mesangium. The description is based mainly on studies of superficial glomeruli of the rat kidney. The contractile apparatus of mesangial cells consists of microfilament bundles located predominantly within mesangial cell processes. The thickest microfilament bundles occur in the juxtacapillary mesangial cell processes, which directly abut the glomerular capillaries. The effector structure of mesangial cell contractility is the GBM. Mesangial cell processes are connected to the GBM either directly or through the interposition of extracellular microfibrils. In general, the contractile system of the mesangium interconnects opposing parts of the GBM. This arrangement is particularly obvious in the juxtacapillary processes, which underlie a mechanical connection between the GBM at the two opposing mesangial angles of a single capillary. The geometry and structural composition of the contractile apparatus of the mesangium indeed suggest a static rather than a dynamic function. In conjunction with the GBM, the mesangial contractile apparatus seems capable of supporting sufficient wall tension to counteract the distending forces acting across the capillary walls; the apparatus also seems capable of directly balancing the distending forces on the perimesangial walls. Assuming that mesangial cells are capable of isotonic contractions, the effect of such a contraction on capillary diameter and, consequently, on filtration area would be small.

Actin Cytoskeleton↗
PubMed1974

The glomerular mesangium. II. Studies of macromolecular uptake in nephrotoxic nephritis in rats.

These studies were designed to explore the effects of nephrotoxic serum (NTS) in rats on the uptake and processing by the glomerular mesangium of intravenously administered protein macromolecules (radiolabeled aggregated human IgG, [125I]AHIgG). Measurements of [125I]AHIgG levels in preparations of isolated glomeruli correlated well with qualitative estimates of glomerular IgG deposition seen by immunofluorescent microscopy. Rats given 2 ml NTS received 25 mg/100 g body wt [125I]AHIgG 48 h later and were sacrificed at varying time intervals thereafter. NTS-treated animals demonstrated a marked increase in glomerular uptake of [125I]AHIgG as compared with concurrent controls but a normal ability to clear [125I]AHIgG from the mesangium over 72 hr. Animals given 1.0, 0.5, and 0.25 ml NTS had neither proteinuria nor significant light microscopic changes, yet had increased uptake of [125I]AHIgG of 4.4, 3.0, and 2.1 times control values, respectively at 8 h after the infusion of aggregates. Rats given 1 ml NTS and 12.5, 6.25, and 3.125 mg [125I]AHIgG/100 g body wt had increased glomerular uptake at 8 h, but there was, within both NTS and control groups, a disproportionate decrease in uptake at lower [125I]AHIgG doses. Rats given cobra venom factor (CoF) followed by a NTS shown to be complement dependent (proteinuria reduced by prior complement depletion with CoF) had less mesangial [125I]AHIgG uptake than NTS controls but greater uptake compared with normal controls. CoF itself had no effect on mesangial or reticuloendothelial system [125I]AHIgG uptake. These studies demonstrate a striking change in glomerular mesangial activity after fixation of nephrotoxic antibodies to the glomerular basement membrane, even in the absence of proteinuria and suggest that subtle alterations of the filtration surface can influence mesangial function. The effect of NTS on the mesangium is due, in large part, to the glomerular injury and proteinuria which nephrotoxic antibodies produce.

Animals↗
PubMed1988

Processing of colloidal gold particles in the glomerular mesangium and macula densa of the duck kidney.

Bovine-serum-albumin coated colloidal gold particles were injected intravenously into healthy, adult domestic ducks. The fate of these tracer particles was followed in a time-sequence up to 4.5 days in the renal glomerular mesangium--distal tubule macula densa junction with transmission electron microscopy. The bulk of particle aggregates is 'trapped' in the mesangial channel system, phagocyted by mesangial cells, exocyted back into the mesangial channels, transported extracellularily towards the vascular hilus, rephagocyted by macula densa cells and expelled into the tubular lumen. This process requires about nineteen hours in the experimental model chosen, although it continues to take place to a much lower extent even 4.5 days after administration of the tracer. This mode of macromolecular excretion may be of interest in connection with the pathogenesis of several forms of glomerulonephritis.

Animals↗
PubMed1972

The glomerular mesangium. I. Kinetic studies of macromolecular uptake in normal and nephrotic rats.

This study was designed to define quantitatively the function of the rat glomerular mesangium in the uptake and processing of intravenously administered protein macromolecules (radiolabeled aggregated human IgG, AHIgG-(125)I), to relate this function to that of the general reticuloendothelial system, and to examine the effects of increased glomerular permeability to protein on the mesangial cell system.Mesangial localization of human IgG as demonstrated by immunofluorescent microscopy showed good correlation with concentrations of AHIgG-(125)I in preparations of isolated glomeruli. In normal rats the concentrations of AHIgG-(125)I in glomeruli were similar to those of lung, liver, and spleen and demonstrated a rapid decrease with increasing time intervals after aggregate administration. In rats given aminonucleoside of puromycin a marked increase in mesangial uptake of aggregates was found while studies of nephrotic lungs, liver, spleen, and blood showed no such differences. Glomerular levels of AHIgG-(125)I in aminonucleoside animals could not be correlated with the quantity of proteinuria. Nephrotic and control animals given unaggregated human IgG showed little glomerular localization by immunofluorescent microscopy; no difference in the concentration of this protein in nephrotic as compared to control glomerular isolates was found.Thus, the mesangium in normal animals functions in a manner analogous to that of the general reticuloendothelial system. In nephrotic rats the mesangial uptake of macromolecules is makedly increased, a finding not observed in other tissues.

Animals↗