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Results for “KIDNEY GLOMERULI”

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At least 19 recordsLinked to original sources
PubMed1998

Paracrine PDGF-B/PDGF-Rbeta signaling controls mesangial cell development in kidney glomeruli.

Kidney glomerulus mesangial cells fail to develop in mice carrying targeted null mutations in the platelet-derived growth factor (PDGF)-B or PDGF-Rbeta genes. We have examined the pattern of expression of these genes and smooth muscle markers during kidney development, to address the possible mechanisms underlying the mutant phenotypes. In wild-type embryos, PDGF-B was expressed in vascular endothelial cells, particularly in capillary endothelial cells in the developing glomeruli, whereas PDGF-Rbeta was found in perivascular mesenchymal cells in the developing renal cortex. In the course of glomerular development, small groups of PDGF-Rbeta and desmin-expressing cells collected in the 'S'-shaped and early cup-shaped vesicles, and at later stages such cells were found in the glomerular mesangium. In PDGF-B or -Rbeta null embryos, some PDGF-Rbeta/desmin or desmin-positive cells, respectively, were seen in early cup-shaped vesicles, but fewer than in the wild type, and further development of the mesangium failed. In mouse chimeras composed of PDGF-Rbeta +/+ and -/- cells, the Rbeta-/- cells failed to populate the glomerular mesangium. Our results show that while the mesangial cell lineage is specified independently of PDGF-B/Rbeta, these molecules provide critical permissive signals in mesangial cell development. We propose a model in which mesangial cells originate from PDGF-Rbeta-positive progenitors surrounding the developing glomerular afferent and efferent arterioles, and are co-recruited in response to PDGF-B during angiogenic formation of the glomerular capillary tuft.

Animals↗
PubMed1979

Prostaglandin synthesis in isolated rat kidney glomeruli.

Isolated rat kidney glomeruli converted octatritiated arachidonic acid to several prostaglandins whose production was inhibited by meclofenamate. These were, in order of decreasing abundance, prostaglandin F2 alpha, prostaglandin E2, 6-oxo-prostaglandin F1 alpha, thromboxane B2, and prostaglandin D2. These products were identified by thin-layer chromatography, before and after treatment with potassium hydroxide or sodium borohydride. Prostaglandins F2 alpha and E2 were also determined by radioimmunoassay. The major product made by glomeruli was an unidentified substance(s), whose appearance was partially inhibited by meclofenamate, and was likely to be a hydroxylated fatty acid(s). The specific activity of glomerular fatty acid cyclo-oxygenase (EC 1.14.99.1), based on radioimmunoassay for prostaglandins E2 and F2 alpha, was 10- to 40-fold higher than that of cortical tubular enzyme. These data demonstrate that glomeruli have the capability of synthesizing an array of end-products from arachidonic acid. These prostaglandins may exert important physiologic effects, because renin secretion and arteriolar resistance are regulated by the glomerulus and the afferent and efferent arterioles.

Animals↗
PubMed1985

Aromatic L-amino acid decarboxylase, dopamine beta-hydroxylase, monoamine oxidase, malondialdehyde, and acid phosphatase in rat brain capillaries and kidney glomeruli in experimental hypertension.

Some metabolic consequences of experimental hypertension on rat brain capillaries and kidney glomeruli have been studied in rats made hypertensive by a combination of deoxycorticosterone acetate injection and elevated salt intake (DOCA-salt hypertension) and isoproterenol injection. Enzyme activities were studied in vitro to ascertain directly or indirectly any changes in the metabolism of catecholamines and prostaglandins, and lysosomal integrity under conditions of experimental hypertension. Experimental hypertension was accompanied by an elevation in the activities of aromatic L-aminoacid decarboxylase, dopamine beta-hydroxylase, and malondialdehyde concentration, both in the brain capillaries and kidney glomeruli of rats. On the other hand, monoamine oxidase activity increased in brain capillaries but decreased in kidney glomeruli. Acid phosphatase activity increased marginally in kidney glomeruli but decreased significantly in brain capillaries. The catecholamine-synthesizing potential appears to have been augmented in both the tissue capillaries with a compensatory increase in the degrading enzyme activity in the brain capillaries of hypertensive rats. The absence of such an increase and an actual decrease in the monoamine oxidase activity in the kidney glomeruli may be responsible for the sustained maintenance of the hypertensive state. Increased malondialdehyde concentration may be due to the stimulation of the prostaglandin metabolism by the augmented catecholamine metabolism.

Acid Phosphatase↗
PubMed2001

[Morphometric study of the human right and left kidney glomeruli--age factors].

80 autopsy kidneys were studied in healthy people of both sexes. All of them had only one artery. The material was distributed into 4 age groups: first period of maturity (21-35 Ys old women, 22-35 Ys old men), second period of maturity (36-55 Ys old women, 36-60 Ys old men), pre-senile (56-74 Ys old women, 61-74 Ys old men) and senile (75-90 Ys old people) age. Statistically significant difference was not determined in none of age groups during comparison of the results of morphometric study of right and left kidney glomeruli.

Adult↗
PubMed1997

Adenovirus-mediated beta-galactosidase gene delivery to the liver leads to protein deposition in kidney glomeruli.

The many cell types of the kidney, precisely arranged, allow this organ to perform its complex physiologic functions. However, this architectural complexity makes gene transfer into the kidney difficult. One approach to delivering a therapeutic protein to the kidney is to transfer a gene to a non-renal tissue. Release of the protein into the circulation might then result in deposition in the kidney, if the protein has the appropriate molecular properties. In this study, we found that parenterally administered replication deficient adenovirus carrying the beta-galactosidase gene resulted in intense beta-galactosidase gene expression in hepatocytes. As a result of immune attack on transduced hepatocytes, beta-galactosidase protein from these cells is released into the circulation, transported, and deposited almost exclusively in kidney glomeruli. Intense beta-galactosidase activity was noted in both kidneys with a peak at two weeks following viral administration, concurrent with loss of beta-galactosidase positive hepatocytes. Consistent with our hypothesis of protein transfer, no beta-galactosidase mRNA was detected in glomeruli. Moreover, systemically administered protein generated similar glomerular beta-galactosidase activity. Finally, co-administration of murine CTLA4 Ig, an immunomodulator of T cell activation, with the adenovirus protected infected hepatocytes and markedly diminished glomerular beta-galactosidase activity. Collectively, these findings suggest that a therapeutic protein can be "targeted" to the renal glomerulus, utilizing the liver as a gene transfer organ.

Abatacept↗
PubMed1986

[Morphological changes in the kidney glomeruli in gout].

Kidney biopsies from 18 patients with primary gout were studied. Glomerular changes were found in all cases along with alterations in tubuli and vessels and stromal sclerosis. They were characterized by local thickening of basal membranes of capillaries, increase in the mesangial matrix, focal or diffuse proliferation of mesangial and endothelial cells of various degree of severity. Proliferation and activation of endothelial cells, mesangiocytes, podocytes, signs of podocyte damage, were found electron-microscopically. Subendothelial lucid zones were observed in the basal membrane, possibly at the site of uric acid deposits. The above described alterations resemble those in focal mesangio-capillary or mesangial proliferative glomerulonephritis.

Adult↗
PubMed1981

Mixed-function oxidases of 25-hydroxycholecalciferol in isolated chick kidney glomeruli: evidence for nuclear localization.

Pure chick kidney glomeruli and proximal tubular fragments have been isolated by graded sieving through nylon screens. Electron micrographs revealed that, in distinct contrast to proximal epithelial cells, the glomerular epithelial and endothelial cells are essentially devoid of mitochondria. Glomeruli as well as proximal tubular fragments contain the 1 alpha- and 24R-hydroxylases of 25-hydroxycholecalciferol. The level of 1 alpha-hydroxylase activity was the same in both segments of the nephron. However, the tubular fragments contained twice the 24R-hydroxylase activity found in glomeruli. Glomerular nuclei were purified by sucrose gradient sedimentation and used to confirm the association of the 1 alpha-hydroxylase with this kidney organelle. Almost all of the glomerular 1 alpha-hydroxylase activity was found in the nuclear fraction. Two metabolites, which are produced predominantly by the nuclei, are designated N-1 and N-2. Their structural identity remains unknown. The novel presence of the 1 alpha-hydroxylase in the glomerulus may be important in defining the etiology of bone diseases in patients with glomerulonephritis and similar disorders.

24,25-Dihydroxyvitamin D 3↗
PubMed1987

Human kidney glomeruli, with special reference to those in the aged person: scanning electron microscopic study of microvascular corrosion casts.

Blood vascular beds of fetal, adult and aged human kidneys were reproduced with methyl methacrylate and observed with a scanning electron microscope. The kidney glomeruli, including those from the fetal kidneys, had anastomosing capillaries. The glomeruli in the kidneys of an aged person contained many more capillaries which were much more tortuous than those of the adult and fetal kidneys. Furthermore, it was observed that the glomeruli in the kidneys of the aged person usually received tortuous afferent vessels and frequently emitted multiple efferent arterioles. The glomeruli in the juxtamedullary layer of the kidneys of the aged person were rather small in size and contained degenerative capillary networks. This observation suggests that the medulla of the kidneys of the aged is poorly supplied with blood.

Adult↗
PubMed1982

Lipoxygenase activity in rat kidney glomeruli, glomerular epithelial cells, and cortical tubules.

We examined the possibility that renal glomerular and cortical tubular tissue has lipoxygenase activity in addition to the well established cyclo-oxygenase pathway of arachidonic acid metabolism. Homogenized rat kidney glomeruli, in the presence of meclofenamate (33 microM) and divalent cation ionophore A23187 (3 microM), metabolized octatritiated arachidonic acid to 12-hydroxyeicosatetraenoic acid and lesser amounts of 80 and/or 9-hydroxyeicosatetraenoic acid. These products were identified by thin layer chromatography, high performance liquid chromatography, and gas chromatography-mass spectroscopy. In order to rule out the synthesis of hydroxylated fatty acids by platelets and leukocytes entrapped in the glomeruli, we studied lipoxygenase products in glomerular epithelial cells after 9 days in cell culture. Homogenized glomerular epithelial cells converted octatritiated arachidonic acid to 12-hydroxyeicosatetraenoic acid solely. The lipoxygenase activity in cortical tubules was substantially less than in glomeruli and only 12-hydroxyeicosatetraenoic acid was synthesized. The production of hydroxyeicosatetraenoic acid by lipoxygenase inhibitors, nordihydroguaiaretic acid, 5,-homogenized glomeruli, glomerular epithelial cells, and cortical tubules was inhibited by three 8,11,14-eicosatetraynoic acid, and 1-phenyl-3-pyrazolidone. These data demonstrate that there is lipoxygenase activity in rat kidney glomeruli, glomerular epithelial cells and to a lesser extent cortical tubules, and may imply a role of the lipoxygenase products in the regulation of normal glomerular function and inflammatory disease of the kidney.

Animals↗
PubMed1996

Adenovirus-mediated gene transfer into kidney glomeruli using an ex vivo and in vivo kidney perfusion system - first steps towards gene therapy of Alport syndrome.

In order to develop gene therapy for Alport syndrome, we have examined the efficiency of adenovirus-mediated transfer of the beta-galactosidase gene into cultured cells and intact glomeruli in vitro, and developed an organ perfusion system for gene transfer into kidney ex vivo and in vivo. Human endothelial and mesangial cells, as well as isolated human glomeruli, were readily infected and exhibited expression of the reporter gene. Single or multiple injections of the virus solution into the renal artery of pig in vivo did not lead to significant gene transfer and expression of the reporter gene in kidney cells. To increase the exposure time of kidney cells to the virus we perfused kidneys ex vivo and in vivo for up to 12 and 2 h, respectively. The perfusion system consisted of a perfusate container, a peristaltic pump and an artificial membrane lung gassed with carbogen. Using this system, intense expression of the reporter gene could be achieved in up to about 85% of the glomeruli after perfusion of an explanted kidney ex vivo and about the same efficiency of gene transfer could be obtained in glomerular cells after 2-h perfusion in vivo. Some expression was observed in other vascular endothelial cells following the perfusion, but no expression was observed in cells of the Bowman's capsule or epithelial cells of the tubuli. The X chromosome-linked form of Alport syndrome is caused by defects in the gene for the type IV collagen of alpha5 chain, which is primarily expressed in the kidney in glomerular cells. The present results demonstrated that efficient gene transfer can be achieved into glomerular cells, a prerequisite for gene therapy of this disease. The organ perfusion method developed in this study might also be applicable for gene therapy of other diseases.

Adenoviruses, Human↗
PubMedDate not supplied

Immunocharacterization of protein kinase C isoenzymes in rat kidney glomeruli, and cultured glomerular epithelial and mesangial cells.

Protein kinase C (PKC) is a key enzyme in the signalling pathways that regulate glomerular functions. To understand the role of PKC in renal homeostasis, the expression and localization of PKC isoenzymes have been investigated. The isoforms of PKC present in rat kidney glomeruli, primary cultures and cell lines of glomerular epithelial and mesangial cells, were identified by immunoblot analysis with isotype-specific antibodies. Glomeruli were isolated from rat kidney cortex by differential sieving and found to express five PKC isoenzymes, PKC-alpha, -beta, -delta, -epsilon and -zeta. No PKC-gamma isoenzyme was detected. Outgrowth of cells from isolated glomeruli after 5 days in culture, considered to be mainly epithelial in nature, displayed strong immunoreactivity to PKC-alpha, -delta, -epsilon and zeta isoenzymes. No PKC-beta and -gamma isoforms were detectable. Outgrowth from isolated glomeruli after 21 days of culture, considered to be mainly mesangial cells, similarly expressed PKC-alpha, -delta, -epsilon and -zeta isotypes, but not PKC-beta and -gamma isoforms. The PKC isoenzyme content of a stable cell line of rat kidney glomerular parietal epithelial cells was also characterized. We have demonstrated previously that a cloned rat mesangial cell line expresses PKC-alpha, -delta, -epsilon and -zeta isoenzymes. Here we report that a cloned parietal epithelial cell line also expressed PKC-alpha, -delta, -epsilon and -zeta isoforms. No beta- and gamma-isoenzymes of PKC were detected. Subcellular distribution of PKC isotypes displayed clear differences, depending on the cell type and the isoenzyme examined. Phorbol 12-myristate 13-acetate stimulation of PKC caused down-regulation of PKC-alpha, -delta and -epsilon isoenzymes in epithelial and mesangial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1980

Effects of age and dietary restriction on the kidney glomeruli of mice: observations by scanning electron microscopy.

A study was undertaken to examine, by scanning electron microscopy (SEM), the kidney glomeruli of control mice 1 mo, 10 mo, and 24 mo of age, as well as dietarily restricted mice 10 mo and 24 mo of age. One month old female C57BL/6J mice were offered one of the following: 1) a control diet containing 24% protein fed ad lib; 2) the control diet fed on alternate days (intermittently fed); or 3) a diet containing 4% protein fed ad lib. Animals were sacrificed, by aldehyde perfusion at 1 mo, 10 mo, and 24 mo of age. The kidneys were sliced and prepared for SEM. There was a significant age-related increase in glomerular diameter and amount of microvilli on the podocyte surface (microvillus index). Although the diameters of the podocytes increased approximately 20% with age, these differences were not statistically significant. Feeding a 4% protein diet resulted in smaller diameters of glomeruli and podocytes as well as smaller microvilli indices as compared to those of control animals. Although similar differences were observed in the kidneys of intermittently fed animals, only the microvillus index was statistically significant. Therefore, dietary manipulations, which have been shown to increase life span, result in marked morphological differences when compared to control animals.

Aging↗
PubMed2005

Ischemia-reperfusion injury stimulates gelatinase expression and activity in kidney glomeruli.

Although ischemia remains the leading cause of acute renal failure in humans, there is little information on the expression and activities of gelatinases of kidney glomeruli during ischemia-reperfusion injury. In this study, we used a unilateral ischemia-reperfusion model to investigate the activity and expression of gelatinases in glomeruli during acute ischemia. Unilateral ischemia was induced in rats by vascular clamping (30 min) followed by reperfusion (60 min) and isolation of glomeruli. The activity and expression of gelatinase proteins were determined by gelatin zymography and Western blotting. Gelatinase mRNA levels were evaluated by reverse transcriptase-PCR. Ischemia and reperfusion increased serum creatinine levels, hallmark of acute renal failure. Ischemia induced mRNA and protein MMP-2 expression. There was strong stimulation of MMP-9 mRNA, both forms of dimeric MMP-9, and active monomeric MMP-9. In contrast to TIMP-1 decreasing, TIMP-2 protein and mRNA increased during ischemia. During reperfusion, there was a gradual reversal of the MMP-2 and MMP-9 levels and a strong inhibition of TIMP-1 and TIMP-2 at the protein and mRNA levels. Endocytic receptor LRP was increased during ischemia and returned to normal during reperfusion. Expression of MMP-9 docking receptor CD-44 was increased during reperfusion. Finally, ZO-1, an in vivo MMP-9 substrate, was degraded during ischemia, revealing that MMP-9 upregulated during ischemia was functional. Our data suggest that stimulation of gelatinase activity during ischemia could contribute to glomeruli injury, providing new therapeutic targets for acute renal failure in humans. In contrast, elevated monomeric MMP-9 activity due to TIMP-1 decrease during reperfusion may participate to glomerular recovery.

Animals↗
PubMed1991

Identification and localization of pertussis toxin-sensitive GTP-binding proteins in bovine kidney glomeruli.

The vascular tree and the mesangium in the glomerulus respond to various hormones, growth factors, and autonomic signals, leading to generation of second messengers and regulation of ion channels. Guanine nucleotide regulatory proteins (G proteins) mediate these effects in other systems. Glomerular G proteins were studied by immunoblotting and immunohistochemical techniques. Glomeruli were isolated from bovine kidney cortex by differential sieving. Glomerular proteins were resolved by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and nitrocellulose transfers were immunoblotted with antibodies to G proteins. G alpha,common antiserum (P-960) recognized proteins with a molecular mass of 41 to 45 kDa. Antibodies against peptide sequences specific to Gi alpha and Go alpha demonstrated Gi alpha, 1/3 (molecular mass, 39 to 41 kDa), Gi alpha 2 (molecular mass, 40 kDa), and Go alpha (molecular mass, 39 kDa). Presence of these proteins was further confirmed by pertussis toxin-catalyzed ADP ribosylation of protein(s) with a molecular mass of 39 to 41 kDa in the glomeruli. Immunohistochemical staining of frozen sections from bovine kidney cortex revealed the presence of Gi alpha 2 in capillary loop distribution in glomeruli and interstitium, but Gi,1/3 or Go could not be demonstrated. The pattern of immunofluorescence with Gi alpha 2 antiserum suggested localization of Gi alpha 2 to the endothelium in glomerular and interstitial vasculature. The novel finding of Go in glomeruli requires localization of Go to specific cells and determination of its role in glomerular physiology. In conclusion, these studies demonstrate that bovine kidney glomeruli express alpha subunits of pertussis toxin-sensitive GTP-binding proteins Gi,1/3, Gi,2 and Go.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate Ribose↗
PubMed1987

Effect of vasoactive intestinal polypeptide on the cyclic adenosine monophosphate generating system in rat kidney glomeruli and cortical tubules.

The effect of in vitro addition of vasoactive intestinal polypeptide (VIP) on the 3'-5'-cyclic adenosine monophosphate (cAMP) generating system in rat kidney glomeruli and cortical tubules was studied. VIP did not stimulate cAMP accumulation in glomeruli; but VIP did stimulate, specifically and in a dose-dependent manner, cAMP concentrations in tubular membranes with the addition of GTP. These results are consistent with the existence of a functionally active VIP receptor coupled to adenylate cyclase in rat kidney cortical tubules.

Animals↗
PubMed1995

Increased phosphorylation of focal adhesion kinase in diabetic rat kidney glomeruli.

Altered extracellular matrix production by the glomerular mesangium is a feature of diabetes mellitus. Matrix proteins, including fibronectin, via interaction with cell-surface receptors (the integrins) may activate intracellular pathways such as prostaglandin production, shown previously to be stimulated by addition of fibronectin to glomerular cores. However, the signalling pathways involved are unclear. An intracellular tyrosine kinase (focal adhesion kinase), associated with focal adhesions, is known to be phosphorylated after interaction with matrix proteins. We now show for the first time, in glomeruli from diabetic rats, that focal adhesion kinase has increased phosphorylation on tyrosine, when compared with non-diabetic control rats. This phosphorylation was labile and disappeared with extended time of sample preparation or digestion of glomeruli to glomerular cores. Cultured mesangial cells, from non-diabetic rats, plated onto fibronectin also showed increased tyrosine phosphorylation of focal adhesion kinase accompanied by a twofold increase in prostaglandin production. However, it may not be possible to replicate fully the diabetic ¿state¿ in vitro merely by use of raised glucose concentrations, as these conditions (for 3 weeks) resulted in decreased focal adhesion kinase phosphorylation, despite increased fibronectin and prostaglandin levels. A role for increased focal adhesion kinase phosphorylation in kidney glomeruli isolated from diabetic rats, and any linkage to intracellular signalling pathways remains to be determined.

Animals↗