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.

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.

Emodin Ameliorates Glucose-Induced Morphologic Abnormalities and Synthesis of Transforming Growth Factor β1 and Fibronectin by Human Peritoneal Mesothelial Cells

2001 ◽  
Vol 21 (3_suppl) ◽  
pp. 41-47 ◽  
Author(s):  
Susan Yung ◽  
Zhi-Hong Liu ◽  
Kar-Neng Lai ◽  
Lei-Shi Li ◽  
Tak-Mao Chan
Keyword(s):  
Growth Factor ◽  
High Glucose ◽  
Glucose Concentration ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Mesothelial Cells ◽  
High Glucose Concentration ◽  
Matrix Synthesis ◽  
Peritoneal Mesothelial Cells ◽  
Human Peritoneal Mesothelial Cells

♦ Objective Excessive synthesis and deposition of matrix proteins by peritoneal mesothelial cells can lead to structural and functional changes in the peritoneal membrane, jeopardizing the long-term efficacy of peritoneal dialysis (PD). Prolonged exposure to high glucose concentrations in PD fluid has been implicated as a major stimulus to matrix accumulation, through the induction of transforming growth factor β1 (TGFβ 1). This study investigated the effect of emodin (3-methyl-1,6,8-trihydroxyanthraquinone) on TGFβ 1 and fibronectin (FN) synthesis in human peritoneal mesothelial cells (HPMCs) under high glucose concentration. ♦ Design The HPMCs were preconditioned in either 5 mmol/L or 30 mmol/L d-glucose for 2 weeks prior to the addition of emodin. Cell viability was assessed by MTT assay and lactate dehydrogenase (LDH) release. Morphology of HPMCs was studied by phase-contrast microscopy. Modulation of TGFβ 1 and FN synthesis at transcription and translation were investigated by reverse transcriptase polymerase chain reaction (RT-PCR), ELISA, and Western blot analysis. ♦ Results When cultured under 30 mmol/L d-glucose, HPMCs demonstrated increased cell volume, multi-nucleation, and denudation of the monolayer, as compared with cells cultured under a physiologic (5 mmol/L) glucose concentration. High glucose concentration induced TGFβ 1 synthesis by HPMCs (217.17 ± 14.88 pg/mL at 5 mmol/L d-glucose vs 370.33 ± 20.67 pg/mL at 30 mmol/L d-glucose, p < 0.0001), and FN synthesis was induced at transcription and translation. Mannitol at 30 mmol/L did not affect HPMC morphology; matrix synthesis was also unaltered. Administration of emodin together with 30 mmol/L d-glucose resulted in amelioration of cell enlargement and exfoliation, and abrogation of TGFβ 1 induction (370.33 ± 20.67 pg/mL for 30 mmol/L d-glucose alone vs 260.50 ± 17.89 pg/mL for 30 mmol/L d-glucose + emodin, p < 0.0001). Synthesis of FN induced by high glucose was also reduced by 40% in the presence of emodin. ♦ Conclusions These findings provide the first evidence that emodin can ameliorate high glucose–induced matrix synthesis in HPMCs by suppression of TGFβ 1. Emodin may thus be useful in preserving peritoneal integrity in PD.

High Glucose Solution and Spent Dialysate Stimulate the Synthesis of Transforming Growth Factor-β1 of Human Peritoneal Mesothelial Cells: Effect of Cytokine Costimulation

1999 ◽  
Vol 19 (3) ◽  
pp. 221-230 ◽  
Author(s):  
Duk-Hee Kang ◽  
Young-Sook Hong ◽  
Hyun Joung Lim ◽  
Jin-Hee Choi ◽  
Dae-Suk Han ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Protein Secretion ◽  
High Glucose ◽  
Transforming Growth Factor ◽  
Glucose Solution ◽  
Mesothelial Cells ◽  
Peritoneal Dialysate ◽  
Peritoneal Mesothelial Cells ◽  
Spent Dialysate ◽  
Human Peritoneal Mesothelial Cells

Objective To investigate the effect of high glucose and spent peritoneal dialysate on the transforming growth factor-β1 (TGFβ1) synthesis of cultured human peritoneal mesothelial cells (HPMCs) and to examine the effect of costimulation with high glucose or spent dialysate, and cytokines, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNFα) on TGFβ1 synthesis of HPMCs. Design HPMCs were exposed to different concentrations of glucose (30, 60, and 90 mmol/L) or spent peritoneal dialysate for 48 hours in the absence or presence of IL-1β (1 ng/mL) and TNFα (1 ng/mL). TGFβ1 mRNA expression was assessed by Northern blot analysis and TGFβ1 protein release by Western blot analysis and enzymelinked immunosorbent assay (ELISA). Results Exposure of HPMCs to high glucose conditions (30, 60, and 90 mmol/L of D-glucose) induced 2.3-, 3.6-, and 4.0-fold increases in TGFβ1 mRNA expression of HPMC with enhanced TGFβ1 protein synthesis and secretion into the media, whereas there were no significant changes in TGFβ1 synthesis with equimolar concentrations of D-mannitol. Incubation with spent dialysate also significantly increased TGFβ1 mRNA expression and protein secretion compared to control media ( p < 0.05). Stimulation with IL-1β (1 ng/mL) or TNFα (1 ng/mL) resulted in a significant increase in TGFβ1 mRNA expression after 48 hours: 2.7 and 2.1 times the control level, respectively. However, TNFα-induced increase in TGFβ1 mRNA expression was not translated into TGFβ1 protein secretion, while IL-1β stimulation induced a significant increase in TGFβ1 protein secretion as well as TGFβ1 mRNA expression. Combined stimulation by high glucose or spent dialysate, together with IL-1β or TNFα, showed a greater increase in TGFβ1 mRNA expression and protein secretion compared to stimulation by high glucose or spent dialysate alone. Conclusion Our results clearly show that high glucose solution and spent dialysate themselves might be sufficient to stimulate the production of TGFβ1 by peritoneal mesothelial cells. In peritoneal dialysis patients, this state of chronic induction of TGFβ1 is further exacerbated in the presence of peritonitis because of the stimulatory effect of proinflammatory cytokines, resulting in augmented TGFβ1 synthesis, thus promoting peritoneal fibrosis.

scholarly journals High glucose and hyperosmolality stimulate hepatocyte growth factor secretion from cultured human mesangial cells

Diabetologia ◽  
1994 ◽  
Vol 37 (5) ◽  
pp. 533-535 ◽  
Author(s):  
J. J. Couper ◽  
A. Ferrante ◽  
K. D. Littleford ◽  
R. T. L. Couper ◽  
T. Nakamura
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
High Glucose ◽  
Mesangial Cells ◽  
Human Mesangial Cells ◽  
Hepatocyte Growth ◽  
Factor Secretion ◽  
Growth Factor Secretion

scholarly journals High glucose promotes TGF-β1 production by inducing FOS expression in human peritoneal mesothelial cells

2015 ◽  
Vol 20 (1) ◽  
pp. 30-38 ◽  
Author(s):  
Keiko Kokoroishi ◽  
Ayumu Nakashima ◽  
Shigehiro Doi ◽  
Toshinori Ueno ◽  
Toshiki Doi ◽  
...  
Keyword(s):  
High Glucose ◽  
Mesothelial Cells ◽  
Peritoneal Mesothelial Cells ◽  
Human Peritoneal Mesothelial Cells ◽  
Fos Expression ◽  
Tgf Β1

scholarly journals Effect of lactate as a peritoneal dialysis fluid buffer on rat peritoneal mesothelial cells

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Chieko Higuchi ◽  
Junko Kuriyama ◽  
Hiroshi Sakura
Keyword(s):  
Peritoneal Dialysis ◽  
Growth Factor ◽  
Mesothelial Cells ◽  
Matrix Metalloproteinase 2 ◽  
Dialysis Fluid ◽  
Mesenchymal Transition ◽  
Peritoneal Mesothelial Cells ◽  
Peritoneal Dialysis Fluid ◽  
E Cadherin

Abstract Background Neutral, low-glucose degradation product (GDP) peritoneal dialysis fluid (PDF) is less damaging to the peritoneum than conventional PDF but is still insufficient for biocompatibility. One remaining issue is the problem of buffering. Methods Using cultured rat peritoneal mesothelial cells (PMCs), the present study examined the difference between the effects of neutral low-GDP lactate PDF and neutral low-GDP bicarbonate/lactate PDF on cells. The effects of lactate stimulation on these cells were also examined. Results Lactate PDF enhanced mRNA expressions of α-smooth muscle actin (αSMA) and type 1 and type 3 collagens and lowered expression of e-cadherin mRNA in PMCs compared to bicarbonate/lactate PDF. Lactate stimulation increased mRNA expressions of αSMA, matrix metalloproteinase 2 (MMP2), and basic fibroblast growth factor (bFGF) and suppressed e-cadherin mRNA expression. Transforming growth factor (TGF)-β1 and TGF-β2 and collagen type 1 and 3 mRNA expressions were also enhanced by lactate stimulation. Conclusions These results suggest that lactate as a PDF buffer may act on PMCs to promote epithelial-mesenchymal transition (EMT) and production of TGF-β, bFGF, and collagen.

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.

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