scholarly journals Glucose and Prednisolone Alter Basic Fibroblast Growth Factor Expression in Peritoneal Mesothelial Cells and Fibroblasts

2001 ◽  
Vol 12 (12) ◽  
pp. 2787-2796
Author(s):  
Satoshi Ogata ◽  
Noriaki Yorioka ◽  
Nobuoki Kohno
Keyword(s):  
Growth Factor ◽  
High Glucose ◽  
Neutralizing Antibody ◽  
Mesothelial Cells ◽  
Fibroblast Growth ◽  
Glucose Medium ◽  
Peritoneal Fibrosis ◽  
Peritoneal Mesothelial Cells ◽  
High Glucose Medium ◽  
Cells Cultured

ABSTRACT. The mechanism of peritoneal fibrosis in patients on continuous ambulatory peritoneal dialysis is poorly understood. The production of basic fibroblast growth factor (bFGF) by human peritoneal mesothelial cells cultured in high glucose medium was investigated, and the behavior of peritoneal fibroblasts, as well as the inhibitory effect of prednisolone, was assessed. Reverse transcriptase-PCR and immunocytochemistry showed the expression of glucocorticoid receptors in mesothelial cells. The semiquantitative reverse transcriptase-PCR showed that high glucose medium (4.0%) increased bFGF mRNA by 2.5-fold relative to control medium (0.1% glucose), with 83% suppression of the increase by 1 μM prednisolone. The bFGF protein level in culture supernatant was also increased by 1.5-fold in high glucose medium, with this change showing 45% suppression by 1 μM prednisolone. These effects of prednisolone were prevented by a glucocorticoid receptor antagonist (RU486) in a concentration-dependent manner. The proliferation of peritoneal fibroblasts was increased 1.9-fold by the supernatant of mesothelial cells cultured in high glucose medium, with 85% suppression by 1 μM prednisolone and suppression to 16% below basal proliferation by an anti-bFGF neutralizing antibody (10 μg/ml), whereas proliferation showed a concentration-dependent increase on addition of an anti-transforming growth factor beta-neutralizing antibody. Recombinant bFGF (50 to 1000 pg/ml) likewise caused a concentration-dependent increase of peritoneal fibroblast proliferation and fibronectin release by these cells was also increased (at 50 to 5000 pg/ml). These results suggest the potential importance of bFGF for initiation of peritoneal fibrosis and the possible efficacy of glucocorticoids for preventing such fibrosis in patients receiving peritoneal dialysis.

The John F. Maher Recipient Lecture 2004: Rage in the Peritoneum

2005 ◽  
Vol 25 (1) ◽  
pp. 8-11 ◽  
Author(s):  
An S. De Vriese
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
High Glucose ◽  
Transforming Growth Factor ◽  
Degradation Products ◽  
Mesothelial Cells ◽  
Cell Surface Receptor ◽  
Peritoneal Membrane ◽  
Peritoneal Fibrosis ◽  
Mesenchymal Transition

Several conditions in the peritoneal membrane of peritoneal dialysis (PD) patients promote the accumulation of advanced glycation end-products (AGEs), that is, the uremic state, exposure to high glucose concentrations, and exposure to glucose degradation products (GDPs). AGEs exert some of their biologic actions through binding with a cell surface receptor, termed RAGE. Interaction of AGEs with RAGE induces sustained cellular activation, including the production of the fibrogenic growth factor, transforming growth factor-beta (TGF-β). TGF-β is pivotal in the process of epithelial-to-mesenchymal transition, through which cells of epithelial origin acquire myofibroblastic characteristics. Myofibroblasts are involved in virtually all conditions of pathological fibrosis. Submesothelial fibrosis is an important feature in peritoneal biopsies of PD patients, especially of those with clinical problems. We therefore examined the role of RAGE in peritoneal fibrosis, in an animal model of uremia, of high glucose exposure, and of peritoneal dialysate exposure. All three models were characterized by accumulation of AGEs, upregulation of RAGE, and fibrosis. Antagonism of RAGE prevented the upregulation of TGF-β and fibrosis in the peritoneal membrane. We further examined the underlying mechanism of peritoneal fibrosis in the uremic model. Prominent myofibroblast transdifferentiation of mesothelial cells was identified by co-localization of cytokeratin and α-smooth muscle actin in submesothelial and interstitial fibrotic tissue. Antagonism of RAGE prevented conversion of mesothelial cells to myofibroblasts in uremia. In conclusion, we hypothesize that accumulation of AGEs in the peritoneal membrane, as a consequence of the uremic environment, chronic exposure to high glucose, and exposure to GDPs, results in an increased expression of RAGE. The interaction of AGEs with RAGE induces peritoneal fibrosis by virtue of upregulation of TGF-β and subsequent conversion of mesothelial cells into myofibroblasts.

Effect of Jinmaitong (筋脉通) serum on the proliferation of rat Schwann cells cultured in high glucose medium

2008 ◽  
Vol 14 (4) ◽  
pp. 293-297 ◽  
Author(s):  
Ling Qu ◽  
Xiao-chun Liang ◽  
Hong Zhang ◽  
Qun-li Wu ◽  
Lian-qing Sun ◽  
...  
Keyword(s):  
Schwann Cells ◽  
High Glucose ◽  
Glucose Medium ◽  
High Glucose Medium ◽  
Cells Cultured

Possible Role of Hepatocyte Growth Factor in Regeneration of Human Peritoneal Mesothelial Cells

2005 ◽  
Vol 28 (2) ◽  
pp. 141-149 ◽  
Author(s):  
Y. Naiki ◽  
K. Matsuo ◽  
T. Matsuoka ◽  
Y. Maeda
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
High Glucose ◽  
Glucose Solution ◽  
Mesothelial Cells ◽  
Matrix Metalloproteinase 2 ◽  
High Concentration ◽  
Peritoneal Mesothelial Cells ◽  
Human Peritoneal Mesothelial Cells ◽  
Hepatocyte Growth

Human peritoneal mesothelial cells (HPMCs) play an important role in peritoneal functions. During long term peritoneal dialysis, it has been reported that HPMCs are damaged by high glucose solution via the signal of transforming growth factor (TGF)- ß1 produced by HPMCs. In this study, we focused on the effect of hepatocyte growth factor (HGF), known as an anti-fibrotic and anti-TGF-ß1 agent, on HPMCs damaged by high glucose solution. HPMCs were isolated from specimens of the omentum from nonuremic patients after informed consent had been obtained. After confirming adhesion for 6 hours, 100 μL of DMEM with 0.5%FCS were added at different concentrations (D-glucose; 6, 30mM) with or without HGF (10, 30, 100 ng/mL) for 48 hours. We examined the effects of a high concentration of glucose and then focused on following four critical points: 1) the production of HGF from HPMCs exposed to a high concentration of glucose, 2) the expression of c-Met on HPMCs, 3) the viability of those cells, and 4) matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of metalloproteinase-2 (TIMP-2). The following significant changes are described herein: high glucose solution and TGF-ß1 i) decreased HGF production from HPMCs and ii) up-regulated expression of c-Met on HPMCs, and addition of HGF iii) restored viability of HPMCs damaged by glucose, iv) suppressed TGF-ß1 production by HGF, and v) induced up-regulation of MMP-2 and decreased TIMP-2 production by HPMCs. Levels of HGF decreased by high concentrations of glucose in the peritoneal cavity may induce the loss of HPMCs and thereby result in peritoneal fibrosis. These results suggest that HGF is an effective agent in the regeneration of peritoneal membrane damaged by high glucose solution.

EndothelinB Receptor Blocker Inhibits High Glucose-Induced Synthesis of Fibronectin in Human Peritoneal Mesothelial Cells

2006 ◽  
Vol 26 (3) ◽  
pp. 393-401 ◽  
Author(s):  
Miyuki Shimizu ◽  
Yoshitaka Ishibashi ◽  
Fumika Taki ◽  
Hideki Shimizu ◽  
Ichiro Hirahara ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Mrna Expression ◽  
Real Time ◽  
High Glucose ◽  
Mesothelial Cells ◽  
Peritoneal Fibrosis ◽  
Peritoneal Mesothelial Cells ◽  
Protein Levels ◽  
Human Peritoneal Mesothelial Cells

Background Long-term peritoneal dialysis using glucose-based dialysates is associated with peritoneal fibrosis. The object of this study was to investigate the hypothesis that endothelin (ET)-1, which is known to play an important role in various fibrotic diseases, may also be involved in peritoneal fibrosis using human peritoneal mesothelial cells (HPMC). Methods HPMC were cultured with 4% d- or l-glucose, or loaded with 10 nmol/L ET-1. In some experiments, the ETA receptor antagonist BQ-123, the ETB receptor antagonist BQ-788, and antioxidants 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL) and diphenyleneiodium chloride (DPI) were used. mRNA expression of ET-1, ETA receptor, ETB receptor, and fibronectin (FN) was analyzed by real-time polymerase chain reaction (real-time PCR). The protein levels for FN and ET-1 were measured by ELISA. CM-H2DCFDA-sensitive reactive oxygen species (ROS) were evaluated by flow cytometry. Results d-Glucose significantly induced mRNA expression of ET-1 and the ETB receptor but not the ETA receptor. FN production under high glucose conditions was inhibited by BQ-788. ET-1 directly stimulated HPMC to increase mRNA expression of FN and CM-H2DCFDA-sensitive ROS production. BQ-788, TEMPOL, and DPI inhibited mRNA expression of FN induced by ET-1. Conclusion The present study suggests that high-glucose-induced FN synthesis is mediated by the ET-1/ETB receptor pathway and, therefore, an ETB receptor antagonist may be useful in preventing FN production in HPMC.

scholarly journals Effect of Glucose on Intercellular Junctions of Cultured Human Peritoneal Mesothelial Cells

2000 ◽  
Vol 11 (11) ◽  
pp. 1969-1979
Author(s):  
TAKAFUMI ITO ◽  
NORIAKI YORIOKA ◽  
MASAO YAMAMOTO ◽  
KATSUKO KATAOKA ◽  
MICHIO YAMAKIDO
Keyword(s):  
Peritoneal Dialysis ◽  
High Glucose ◽  
Transforming Growth Factor ◽  
Intercellular Junctions ◽  
Neutralizing Antibody ◽  
Transforming Growth Factor Β ◽  
Mesothelial Cells ◽  
Peritoneal Mesothelial Cells ◽  
Peritoneal Dialysis Fluid ◽  
Human Peritoneal Mesothelial Cells

Abstract. During continuous ambulatory peritoneal dialysis, the peritoneum is directly and continuously exposed to unphysiologic peritoneal dialysis fluid; the resulting mesothelial damage has been suggested to cause loss of ultrafiltration and dialysis efficacy. The present study investigated the effect of a high glucose concentration on cultured human peritoneal mesothelial cells to clarify the cause of decreased dialysis efficacy during prolonged peritoneal dialysis. High glucose caused a concentration-dependent decrease in cell proliferation, damage to the intercellular junctions, and excess production of transforming growth factor-β (TGF-β). The levels of intercellular junctional proteins (ZO-1, E-cadherin, and β-catenin) were decreased, and immuno-staining by anti—ZO-1 and anti— β-catenin antibodies became weaker and often discontinuous along the cell contour. Mannitol had similar but weaker effects at the same osmolality, and an anti—TGF-β neutralizing antibody reduced the effects of high glucose. Therefore, these effects were induced not only by glucose itself but also by hyperosmolality and by a glucose-induced increase of TGF-β. These findings suggest that the peritoneal mesothelium is damaged by prolonged peritoneal dialysis using high glucose dialysate and that impairment of the intercellular junctions of peritoneal mesothelial cells by high glucose dialysate induces peritoneal hyperpermeability and a progressive reduction in dialysis efficacy.

scholarly journals SGLT2 Inhibition by Intraperitoneal Dapagliflozin Mitigates Peritoneal Fibrosis and Ultrafiltration Failure in a Mouse Model of Chronic Peritoneal Exposure to High-Glucose Dialysate

Biomolecules ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1573
Author(s):  
Michael S. Balzer ◽  
Song Rong ◽  
Johannes Nordlohne ◽  
Jan D. Zemtsovski ◽  
Sonja Schmidt ◽  
...  
Keyword(s):  
High Glucose ◽  
Structural Changes ◽  
Glucose Transporter ◽  
Transforming Growth Factor ◽  
Sglt2 Inhibitor ◽  
Mesothelial Cells ◽  
Peritoneal Fibrosis ◽  
Peritoneal Mesothelial Cells ◽  
Ultrafiltration Failure

Peritoneal dialysis (PD) is limited by glucose-mediated peritoneal membrane (PM) fibrosis, angiogenesis, and ultrafiltration failure. Influencing PM integrity by pharmacologically targeting sodium-dependent glucose transporter (SGLT)-mediated glucose uptake has not been studied. In this study, wildtype C57Bl/6N mice were treated with high-glucose dialysate via an intraperitoneal catheter, with or without addition of selective SGLT2 inhibitor dapagliflozin. PM structural changes, ultrafiltration capacity, and peritoneal equilibration testing (PET) status for glucose, urea, and creatinine were analyzed. Expression of SGLT and facilitative glucose transporters (GLUT) was analyzed by real-time PCR, immunofluorescence, and immunohistochemistry. Peritoneal effluents were analyzed for cellular and cytokine composition. We found that peritoneal SGLT2 was expressed in mesothelial cells and in skeletal muscle. Dapagliflozin significantly reduced effluent transforming growth factor (TGF-β) concentrations, peritoneal thickening, and fibrosis, as well as microvessel density, resulting in improved ultrafiltration, despite the fact that it did not affect development of high-glucose transporter status. In vitro, dapagliflozin reduced monocyte chemoattractant protein-1 release under high-glucose conditions in human and murine peritoneal mesothelial cells. Proinflammatory cytokine release in macrophages was reduced only when cultured in high-glucose conditions with an additional inflammatory stimulus. In summary, dapagliflozin improved structural and functional peritoneal health in the context of high-glucose PD.

scholarly journals Testosterone Protects Against Glucotoxicity-Induced Apoptosis of Pancreatic β-Cells (INS-1) and Male Mouse Pancreatic Islets

Endocrinology ◽  
2013 ◽  
Vol 154 (11) ◽  
pp. 4058-4067 ◽  
Author(s):  
Wanthanee Hanchang ◽  
Namoiy Semprasert ◽  
Thawornchai Limjindaporn ◽  
Pa-thai Yenchitsomanus ◽  
Suwattanee Kooptiwut
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
High Glucose ◽  
Male Mouse ◽  
Glucose Medium ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Stress Markers ◽  
High Glucose Medium ◽  
Cells Cultured

Male hypogonadism associates with type 2 diabetes, and T can protect pancreatic β-cells from glucotoxicity. However, the protective mechanism is still unclear. This study thus aims to examine the antiapoptotic mechanism of T in pancreatic β cells cultured in high-glucose medium. T (0.0005–2 μg/mL) was added to INS-1 cells cultured in basal glucose or high-glucose media. Then cellular apoptosis, oxidative stress, and cell viability were measured. Endoplasmic reticulum (ER) stress markers and sensors and the antiapoptotic protein (B-cell lymphoma 2) were investigated by real-time PCR and Western blot analysis. ER stress markers were also measured in male mouse pancreatic islet cultured in similar conditions. T (0.05 and 0.5 μg/mL) did not have any effect on apoptosis and viability of INS-1 cells cultured in basal glucose medium, but it could reduce apoptosis and increase viability of INS-1 cells cultured in high-glucose medium. The protective effect of T is diminished by androgen receptor inhibitor. T (0.05 μg/mL) could significantly reduce nitrotyrosine levels, mRNA, and protein levels of the ER stress markers and sensor those that were induced when INS-1 cells were cultured in high-glucose medium. It could also significantly increase the survival proteins, sarco/endoplasmic reticulum Ca2+ ATPase-2, and B-cell lymphoma 2 in INS-1 cells cultured in the same conditions. Similarly, it could reduce ER stress markers and increase sarco/endoplasmic reticulum Ca2+ ATPase protein levels in male mouse pancreatic islets cultured in high-glucose medium. T can protect against male pancreatic β-cell apoptosis from glucotoxicity via the reduction of both oxidative stress and ER stress.

scholarly journals Basic Fibroblast Growth Factor Synthesis by Human Peritoneal Mesothelial Cells

1999 ◽  
Vol 155 (6) ◽  
pp. 1977-1984 ◽  
Author(s):  
Marcus Victor Cronauer ◽  
Sylvia Stadlmann ◽  
Helmut Klocker ◽  
Burghard Abendstein ◽  
Iris Elisabeth Eder ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Mesothelial Cells ◽  
Fibroblast Growth ◽  
Peritoneal Mesothelial Cells ◽  
Human Peritoneal Mesothelial Cells

Effects of Peritoneal Dialysis Solutions on the Secretion of Growth Factors and Extracellular Matrix Proteins by Human Peritoneal Mesothelial Cells

2002 ◽  
Vol 22 (2) ◽  
pp. 171-177 ◽  
Author(s):  
Hunjoo Ha ◽  
Mi Kyung Cha ◽  
Hoo Nam Choi ◽  
Hi Bahl Lee
Keyword(s):  
Peritoneal Dialysis ◽  
Growth Factor ◽  
High Glucose ◽  
Transforming Growth Factor ◽  
Mesothelial Cells ◽  
Dependent Manner ◽  
Peritoneal Mesothelial Cells ◽  
Human Peritoneal Mesothelial Cells ◽  
Dialysis Solutions ◽  
Peritoneal Dialysis Solutions

♦ Objective To compare the effects of different peritoneal dialysis solutions (PDS) on secretion of vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGFβ1), procollagen I C-terminal peptide (PICP), procollagen III N-terminal peptide (PIIINP), and fibronectin by cultured human peritoneal mesothelial cells (HPMC). ♦ Design Using M199 culture medium as control, commercial PDS containing 1.5% or 4.25% glucose and 40 mmol/L lactate [Dianeal 1.5 (D 1.5) and Dianeal 4.25 (D 4.25), respectively; Baxter Healthcare, Deerfield, Illinois, USA]; PDS containing 1.5% or 4.25% glucose with 25 mmol/L bicarbonate and 15 mmol/L lactate [Physioneal 1.5 (P 1.5) and Physioneal 4.25 (P 4.25), respectively; Baxter]; and PDS containing 7.5% icodextrin [Extraneal (E); Baxter] were tested. Growth-arrested and synchronized HPMC were continuously stimulated for 48 hours by test PDS diluted twofold with M199, TGFβ1 1 ng/mL, or different concentrations of icodextrin. VEGF, TGFβ1, and fibronectin secreted into the media were analyzed by ELISA, and PICP and PIIINP by radioimmunoassay. ♦ Results Dianeal 1.5, D 4.25, and P 4.25, but not P 1.5 and E, significantly increased VEGF secretion compared with control M199. D 4.25- and P 4.25-induced VEGF secretion was significantly higher than induction by D 1.5 and P 1.5, respectively, suggesting that high glucose may be involved in the induction of VEGF. Physioneal 1.5- and P 4.25-induced VEGF secretion was significantly lower than induction by D 1.5 and D 4.25, respectively, suggesting a role for glucose degradation products (GDP) in VEGF production. TGFβ1 secretion was significantly increased by D 4.25 and E. Icodextrin increased TGFβ1 secretion in a dose-dependent manner. All PDS tested significantly increased secretion of PIIINP compared with control. D 1.5- and D 4.25-induced PIIINP secretion was significantly higher than P 1.5, P 4.25, and E. Physioneal 4.25-induced PIIINP secretion was significantly higher than P 1.5, again implicating high glucose and GDP in PIIINP secretion by HPMC. There was no significant increase in PICP or fibronectin secretion using any of the PDS tested. Addition of TGFβ1 1 ng/mL into M199 control significantly increased VEGF, PICP, PIIINP, and fibronectin secretion by HPMC. ♦ Conclusions The present study provides direct evidence that HPMC can secrete VEGF, TGFβ1, and PIIINP in response to PDS, and that HPMC may be actively involved in the development and progression of the peritoneal membrane hyperpermeability and fibrosis observed in long-term PD patients. This study also suggests that both high glucose and GDP in PDS may play important roles in inducing VEGF and PIIINP production/secretion by HPMC.

Sign in / Sign up

Export Citation Format

Share Document