Conserved charge of glomerular and mesangial cell proteoglycans: possible role of amino acid-derived sulphate

1992 ◽  
Vol 70 (6) ◽  
pp. 843-852 ◽  
Author(s):  
Douglas M. Templeton ◽  
Aimin Wang
Keyword(s):  
Charge Density ◽  
Mesangial Cells ◽  
Heparan Sulphate ◽  
Cell Types ◽  
Sole Source ◽  
Isolated Glomeruli ◽  
Inorganic Sulphate ◽  
Multifunctional Molecules ◽  
Nontransformed Cell

Sulphation of proteoglycans was studied in isolated glomeruli and cultured rat mesangial cells. Both preparations produced heparan, dermatan, and chondroitin sulphates, recoverable both from the tissue layers and the conditioned media. The proportion of heparan sulphate made by mesangial cells was independent of the age of the culture, but declined in later passage. These preparations differed from several other nontransformed cell types studied to date in that the degree of proteoglycan sulphation was independent of the concentration of inorganic sulphate provided. Even when no exogenous sulphate was added, sulphation-dependent charge density of newly synthesized proteoglycans was conserved. Both isolated glomeruli and cultured mesangial cells produced proteoglycans with 35S-labelled sulphate esters when [35S]methionine was provided as the sole source of labelled sulphate. Conversion of methionine to cysteine and subsequent oxidation of organic sulphate via the sulphinyl pyruvate pathway is the only mechanism known in eukaryotic cells that can account for this observation. We conclude that facile oxidation of sulphur-containing amino acids can contribute to sulphation of glomerular proteoglycans and may serve to sustain the charge density of these multifunctional molecules when the supply of inorganic sulphate is otherwise compromised.Key words: renal glomerulus, proteoglycans, sulphation, heparan sulphate, basement membrane.

Heparin/heparan sulphate binding in the TGF-β cytokine superfamily

2006 ◽  
Vol 34 (3) ◽  
pp. 458-460 ◽  
Author(s):  
C.C. Rider
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Transforming Growth Factor ◽  
Heparan Sulphate ◽  
Transforming Growth Factor Β ◽  
Cell Types ◽  
Binding Properties ◽  
And Migration ◽  
Close Relatives ◽  
Bmp Antagonist

The TGF-β (transforming growth factor-β) cytokine superfamily in mammals contains some 30 members. These dimeric proteins are characterized by a strongly conserved cystine knot-based structure. They regulate the proliferation, differentiation and migration of many cell types, and therefore have important roles in morphogenesis, organogenesis, tissue maintenance and wound healing. Thus far, around one-quarter of these cytokines have been shown to bind to heparin and heparan sulphate. Well-established examples are the TGF-β isoforms 1 and 2, and the BMPs (bone morphogenetic proteins) -2 and -4. In studies in my laboratory, we have shown that GDNF (glial-cell-line-derived neurotrophic factor) and its close relatives neurturin and artemin bind to heparin and heparan sulphate with high affinity. We have reported previously that binding of GDNF is highly dependent on the presence of 2-O-sulphate groups. More recently, we and others have been investigating the heparin/heparan sulphate-binding properties of BMP-7, which is a representative of a distinct BMP subgroup from that of BMPs -2 and -4. Interestingly, several of the various specific BMP antagonist proteins also bind to heparin and heparan sulphate. Much remains to be learnt about the nature and role of glycosaminoglycan interactions in the TGF-β superfamily, but current work suggests that these cytokines do not share a single highly conserved heparin/heparan sulphate-binding site.

The role of endoglin in kidney fibrosis

2014 ◽  
Vol 16 ◽  
Author(s):  
Jose M. Muñoz-Felix ◽  
Barbara Oujo ◽  
Jose M. Lopez-Novoa
Keyword(s):  
Transforming Growth Factor Beta ◽  
Renal Fibrosis ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Cell Types ◽  
Experimental Models ◽  
Kidney Fibrosis ◽  
End Stage

Tubulointerstitial fibrosis and glomerulosclerosis, are a major feature of end stage chronic kidney disease (CKD), characterised by an excessive accumulation of extracellular matrix (ECM) proteins. Transforming growth factor beta-1 (TGF-β1) is a cytokine with an important role in many steps of renal fibrosis such as myofibroblast activation and proliferation, ECM protein synthesis and inflammatory cell infiltration. Endoglin is a TGF-β co-receptor that modulates TGF-β responses in different cell types. In numerous cells types, such as mesangial cells or myoblasts, endoglin regulates negatively TGF-β-induced ECM protein expression. However, recently it has been demonstrated that ‘in vivo’ endoglin promotes fibrotic responses. Furthermore, several studies have demonstrated an increase of endoglin expression in experimental models of renal fibrosis in the kidney and other tissues. Nevertheless, the role of endoglin in renal fibrosis development is unclear and a question arises: Does endoglin protect against renal fibrosis or promotes its development? The purpose of this review is to critically analyse the recent knowledge relating to endoglin and renal fibrosis. Knowledge of endoglin role in this pathology is necessary to consider endoglin as a possible therapeutic target against renal fibrosis.

Abstract 23: Foxd1+ Stromal Cells, the Required Progenitors for Kidney Vascular Development

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Eugene E Lin ◽  
Roberto A Gomez ◽  
Maria-Luisa S Sequeira-Lopez
Keyword(s):  
Stromal Cells ◽  
Mesangial Cells ◽  
Cell Types ◽  
Lineage Tracing ◽  
Arterial Tree ◽  
Mural Cell ◽  
Mural Cells ◽  
Selective Ablation ◽  
Similar Phenotype

The mechanisms underlying the establishment, assembly and maintenance of the renal blood vessels are poorly understood. We have previously suggested using detailed lineage tracing that renal stromal cells, characterized by their early and transient expression of the transcription factor Foxd1 , give rise to the entirety of the mural cell layer of the renal arterial tree and mesangial cells. Mural cells as defined here exclude endothelial cells, which we identified as having a separate precursor, the renal hemangioblast. To define whether Foxd1 cells are the required essential progenitor or whether their role as such could be assumed by other cell types, we used the cre-lox system to generate mice expressing diphtheria toxin subunit A in Foxd1+ cells ( Foxd1-DTA mice ) which resulted in animals with selective ablation of Foxd1+ cells. Kidneys from Foxd1-DTA embryos had a significantly reduced complement of arterial mural cells, lacking smooth muscle cells, perivascular fibroblasts, renin cells and mesangial cells. Interestingly, the few vessels that remained were also abnormal: they originated underneath the kidney capsule and elongated towards the center of the kidney rather than radiating outward from the center of the kidney. In addition, ablation of Foxd1 cells resulted in significantly delayed nephrogenesis and reduction in glomerular number. In conjunction with our previous data showing a similar phenotype upon global deletion of the Foxd1 ,gene, this illustrates the central role of Foxd1 and the cells that express it during early development. We conclude that Foxd1 stromal cells are the required progenitors for the establishment of the mural cells of the kidney arterioles and (via Foxd1 expression) for the proper origin and orientation of the kidney vessels.

Effect of Calcium on the Growth and Differentiation of Cultured Rat Esophageal Epithelial Cells

1982 ◽  
Vol 40 ◽  
pp. 132-133
Author(s):  
W.T. Gunning ◽  
M.R. Marino ◽  
M.S. Babcock ◽  
G.D. Stoner
Keyword(s):  
Epithelial Cells ◽  
Cell Types ◽  
Replication Rate ◽  
Enzymatic Dissociation ◽  
Growth Assay ◽  
Epidermal Growth ◽  
Fetal Bovine ◽  
Esophageal Epithelial Cells ◽  
Cellular Replication

The role of calcium in modulating cellular replication and differentiation has been described for various cell types. In the present study, the effects of Ca++ on the growth and differentiation of cultured rat esophageal epithelial cells was investigated.Epithelial cells were isolated from esophagi taken from 8 week-old male CDF rats by the enzymatic dissociation method of Kaighn. The cells were cultured in PFMR-4 medium supplemented with 0.25 mg/ml dialyzed fetal bovine serum, 5 ng/ml epidermal growth factor, 10-6 M hydrocortisone 10-6 M phosphoethanolamine, 10-6 M ethanolamine, 5 pg/ml insulin, 5 ng/ml transferrin, 10 ng/ml cholera toxin and 50 ng/ml garamycin at 36.5°C in a humidified atmosphere of 3% CO2 in air. At weekly intervals, the cells were subcultured with a solution containing 1% polyvinylpyrrolidone, 0.01% EGTA, and 0.05% trypsin. After various passages, the replication rate of the cells in PFMR-4 medium containing from 10-6 M to 10-3 M Ca++ was determined using a clonal growth assay.

Role of PKC isozymes in water transport in toad urinary bladder

1991 ◽  
Vol 49 ◽  
pp. 302-303
Author(s):  
A.J. Mia ◽  
L.X. Oakford ◽  
T. Yorio
Keyword(s):  
Urinary Bladder ◽  
Apical Membrane ◽  
Membrane Surface ◽  
Protein A ◽  
Cell Types ◽  
Leukemic Cells ◽  
Toad Urinary Bladder ◽  
Pkc Isozymes ◽  
Antibody Labeling

Protein kinase C (PKC) isozymes, when activated, are translocated to particulate membrane fractions for transport to the apical membrane surface in a variety of cell types. Evidence of PKC translocation was demonstrated in human megakaryoblastic leukemic cells, and in cardiac myocytes and fibroblasts, using FTTC immunofluorescent antibody labeling techniques. Recently, we reported immunogold localizations of PKC subtypes I and II in toad urinary bladder epithelia, following 60 min stimulation with Mezerein (MZ), a PKC activator, or antidiuretic hormone (ADH). Localization of isozyme subtypes I and n was carried out in separate grids using specific monoclonal antibodies with subsequent labeling with 20nm protein A-gold probes. Each PKC subtype was found to be distributed singularly and in discrete isolated patches in the cytosol as well as in the apical membrane domains. To determine if the PKC isozymes co-localized within the cell, a double immunogold labeling technique using single grids was utilized.

Role of the 807 C/T Polymorphism of the α2 Gene in Platelet GP Ia Collagen Receptor Expression and Function

1999 ◽  
Vol 81 (06) ◽  
pp. 951-956 ◽  
Author(s):  
J. Corral ◽  
R. González-Conejero ◽  
J. Rivera ◽  
F. Ortuño ◽  
P. Aparicio ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Cell Types ◽  
Receptor Expression ◽  
Case Control Studies ◽  
Platelet Surface ◽  
Vitro Analysis ◽  
And Function ◽  
In Vitro Analysis

SummaryThe variability of the platelet GP Ia/IIa density has been associated with the 807 C/T polymorphism (Phe 224) of the GP Ia gene in American Caucasian population. We have investigated the genotype and allelic frequencies of this polymorphism in Spanish Caucasians. The T allele was found in 35% of the 284 blood donors analyzed. We confirmed in 159 healthy subjects a significant association between the 807 C/T polymorphism and the platelet GP Ia density. The T allele correlated with high number of GP Ia molecules on platelet surface. In addition, we observed a similar association of this polymorphism with the expression of this protein in other blood cell types. The platelet responsiveness to collagen was determined by “in vitro” analysis of the platelet activation and aggregation response. We found no significant differences in these functional platelet parameters according to the 807 C/T genotype. Finally, results from 3 case/control studies involving 302 consecutive patients (101 with coronary heart disease, 104 with cerebrovascular disease and 97 with deep venous thrombosis) determined that the 807 C/T polymorphism of the GP Ia gene does not represent a risk factor for arterial or venous thrombosis.

Role of Transcriptional Read-Through in PRE Activity in Drosophila melanogaster

Acta Naturae ◽  
2016 ◽  
Vol 8 (2) ◽  
pp. 79-86 ◽  
Author(s):  
P. V. Elizar’ev ◽  
D. V. Lomaev ◽  
D. A. Chetverina ◽  
P. G. Georgiev ◽  
M. M. Erokhin
Keyword(s):  
Dna Sequences ◽  
Cell Types ◽  
Transcription Terminator ◽  
Response Elements ◽  
Polycomb Response Elements ◽  
The Individual ◽  
Multicellular Organisms ◽  
Different Cell Types ◽  
Main Factor

Maintenance of the individual patterns of gene expression in different cell types is required for the differentiation and development of multicellular organisms. Expression of many genes is controlled by Polycomb (PcG) and Trithorax (TrxG) group proteins that act through association with chromatin. PcG/TrxG are assembled on the DNA sequences termed PREs (Polycomb Response Elements), the activity of which can be modulated and switched from repression to activation. In this study, we analyzed the influence of transcriptional read-through on PRE activity switch mediated by the yeast activator GAL4. We show that a transcription terminator inserted between the promoter and PRE doesnt prevent switching of PRE activity from repression to activation. We demonstrate that, independently of PRE orientation, high levels of transcription fail to dislodge PcG/TrxG proteins from PRE in the absence of a terminator. Thus, transcription is not the main factor required for PRE activity switch.

Role of inflammation in the development of colorectal cancer

2020 ◽  
Vol 20 ◽  
Author(s):  
Sridhar Muthusami ◽  
R. Ileng Kumaran ◽  
Kokelavani Nampalli Babu ◽  
Sneha Krishnamoorthy ◽  
Akash Guruswamy ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Chronic Inflammation ◽  
Interleukin 1 ◽  
Cell Types ◽  
Model Systems ◽  
Cytokine Gene Expression ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Proinflammatory Molecules

: Chronic inflammation can lead to the development of many diseases including cancer. Inflammatory bowel disease (IBD) that includes both ulcerative colitis (UC) and Crohn's disease (CD) are risk factors for the development of colorectal cancer (CRC). Many cytokines produced primarily by the gut immune cells either during or in response to localized inflammation in the colon and rectum are known to stimulate the complex interactions between the different cell types in the gut environment resulting in acute inflammation. Subsequently, chronic inflammation together with genetic and epigenetic changes has been shown to lead to the development and progression of CRC. Various cell types present in the colon such as enterocytes, Paneth cells, goblet cells and macrophages express receptors for inflammatory cytokines and respond to tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6 and other cytokines. Among the several cytokines produced, TNF-α and IL-1β are the key proinflammatory molecules that play critical roles in the development of CRC. The current review is intended to consolidate the published findings to focus on the role of proinflammatory cytokines, namely TNF-α and IL-1β, on inflammation (and the altered immune response) in the gut, to better understand the development of CRC in IBD, using various experimental model systems, preclinical and clinical studies. Moreover, this review also highlights the current therapeutic strategies available (monotherapy and combination therapy), to alleviate the symptoms or treat inflammationassociated CRC by using monoclonal antibodies or aptamers to block proinflammatory molecules, inhibitors of tyrosine kinases in inflammatory signaling cascade, competitive inhibitors of proinflammatory molecules, and the nucleic acid drugs like small activating RNAs (saRNAs) or microRNA (miRNA) mimics to activate tumor suppressor or repress oncogene/proinflammatory cytokine gene expression.

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