scholarly journals Curcumin ameliorates peritoneal fibrosis via inhibition of transforming growth factor-activated kinase 1 (TAK1) pathway in a rat model of peritoneal dialysis

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Jun-Li Zhao ◽  
Ting Zhang ◽  
Xia Shao ◽  
Jun-Jun Zhu ◽  
Mei-Zi Guo
Keyword(s):  
Peritoneal Dialysis ◽  
Peritoneal Fluid ◽  
Transforming Growth Factor ◽  
Collagen I ◽  
Control Group ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Peritoneal Fibrosis ◽  
Jnk Pathway ◽  
Tgf Β1

Abstract Background Peritoneal fibrosis (PF) remains a serious complication of long-term peritoneal dialysis (PD). The goal of this study was to investigate the anti-fibrotic effects of curcumin on the PF response to PD and its’ mechanism. Methods Male Sprague–Dawley rats were infused with 20 mL of 4.25% glucose-based standard PD fluid for 8 consecutive weeks to establish PF model and then divided into five groups: Control, received sham operation and 0.9% physiological saline; PD, received 4.25% standard PD fluid; Curcumin, PD rats injected intraperitoeally with curcumin for 8 weeks at doses of 10, 20 or 40 mg/kg. Masson’s staining was performed to evaluate the extent of PF. Peritoneal Equilibration Test (PET) was conducted to assess ultrafiltration volume (UFV) and mass transfer of glucose (MTG), quantitative RT-PCR, and immunohistochemistry or western blotting were performed to measure the expression levels of inflammation and fibrosis-associated factors. We also detected the TGF-β1 in peritoneal fluid by ELISA. Results Compared with the control group, the PD rats showed decreased UFV (2.54 ± 0.48 to 9.87 ± 0.78 mL, p < 0.05] and increased MTG (18.99 ± 0.86 to 10.85 ± 0.65 mmol/kg, p < 0.05) as well as obvious fibroproliferative response, with markedly increased peritoneal thickness (178.33 ± 4.42 to 25.26 ± 0.32um, p < 0.05) and higher expression of a-SMA, collagen I and TGF-β1. Treatment with curcumin significantly increased UFV, reduced MTG and peritoneal thickness of PD rats. The elevated TGF-β1 in peritoneal fluid of PD rats was significantly decreased by curcumin. It attenuated the increase in protein and mRNA of TGF-β1, α-SMA and collagen I in peritoneum of PD rats. The mRNA expressions of TAK1, JNK and p38, as well as the protein expressions of p-TAK1, p-JNK and p-p38 in peritoneum of PD rats were reduced by curcumin. Conclusions Present results demonstrate that curcumin showed a protective effect on PD-related PF and suggest an implication of TAK1, p38 and JNK pathway in mediating the benefical effects of curcumin.

scholarly journals Sulodexide Prevents Peritoneal Fibrosis by Downregulating the Expression of TGF-β1 and Its Signaling Pathway Molecules

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Zhiqiang Duan ◽  
Jia Yao ◽  
Nan Duan ◽  
Min Wang ◽  
Shiwei Wang
Keyword(s):  
Peritoneal Dialysis ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Vascular Endothelial Cells ◽  
Inflammatory Factors ◽  
Control Group ◽  
Peritoneal Fibrosis ◽  
Blank Control Group ◽  
Peritoneal Tissue ◽  
Tgf Β1

Peritoneal dialysis is one of the main renal replacement treatments. However, long-term peritoneal dialysis keeps the peritoneum in contact with the sugar-containing nonphysiological peritoneal fluid, which leads to recurrent peritonitis, peritoneal fibrosis, and failure of ultrafiltration. Transforming growth factor-β1 (TGF-β1), related cytokines, and inflammatory factors are closely related to peritoneal fibrosis. Sulodexide (SLX) is a new type of glycosaminoglycan preparation, which is involved in the formation of an anionic charge barrier and can maintain the selective permeability of vascular endothelial cells. In this study, the innovative analysis of SLX specifically prevents the process of peritoneal dialysis peritoneal fibrosis by downregulating the expression of TGF-β1 and its signaling pathway molecules. We randomly divided 30 rats into three groups. The blank control group received no treatment. The peritoneal dialysis model group was injected with 4.25% peritoneal dialysate (PDF) 20 ml daily, and the SLX group was injected with 4.25% PDF 20 ml + sulodexide (SLX) 20 mg/kg daily. After 8 weeks of dialysis, the rats were sacrificed, and the peritoneal function test was performed to determine the amount of glucose transport and ultrafiltration. The thickness of peritoneal per unit area was observed under high magnification. The level of inflammation in peritoneal tissue and the expression of TGF-β1/Smad were detected. The results showed that SLX can significantly improve peritoneal tissue thickening and inflammation, can downregulate the expression of TGF-β1, Smad2, Smad3, and Smad7 in peritoneal tissue, and improve the progression of peritoneal fibrosis.

scholarly journals Hyaluronan decreases peritoneal fluid absorption in peritoneal dialysis.

1997 ◽  
Vol 8 (12) ◽  
pp. 1915-1920
Author(s):  
T Wang ◽  
C Chen ◽  
O Heimbürger ◽  
J Waniewski ◽  
J Bergström ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Peritoneal Fluid ◽  
Protein Transport ◽  
Intraperitoneal Administration ◽  
Control Group ◽  
Fluid Absorption ◽  
Sprague Dawley ◽  
Transfer Coefficients ◽  
Fluid Removal ◽  
Dialysis Solution

Hyaluronan, exhibiting a high resistance against water flow, acts in the tissue as a barrier against rapid changes in water content. To test whether hyaluronan has any effect on the peritoneal fluid and solute transport, and, in particular, on the peritoneal fluid absorption, a 4-h dwell study with an intraperitoneal volume marker (radiolabeled human serum albumin [RISA]) was conducted in 21 male Sprague Dawley rats (three groups, seven rats in each group). Each rat was injected intraperitoneally with 25 ml of 1.36% glucose solution alone (control group), with 0.005% hyaluronan (HA1 group), or with 0.01% hyaluronan (HA2 group). Dialysate and blood samples were taken frequently for analyses of fluid and solute (urea, glucose, and protein) transport. The intraperitoneal volume was calculated from the dilution of RISA with a correction for RISA disappearance from the peritoneal cavity. This study shows that adding hyaluronan to peritoneal dialysis solution significantly (P < 0.01) increased the net peritoneal fluid removal, mainly due to a significant decrease in the peritoneal fluid absorption rate (P < 0.01). The diffusive mass transfer coefficients for glucose, urea, and protein did not differ between the three groups. The peritoneal clearance of urea increased significantly in the two hyaluronan groups compared with the control group, due to the increased net fluid removal in the hyaluronan groups. These results suggest that intraperitoneal administration of hyaluronan during a single peritoneal dialysis exchange may significantly increase the peritoneal fluid and solute removal by decreasing peritoneal fluid absorption.

Does Enalapril Prevent Peritoneal Fibrosis Induced by Hypertonic (3.86%) Peritoneal Dialysis Solution?

2001 ◽  
Vol 21 (2) ◽  
pp. 219-225 ◽  
Author(s):  
Soner Duman ◽  
Ali Ihsan Günal ◽  
Sait Sen ◽  
Gülay Asçi ◽  
Mehmet Özkahya ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Transforming Growth Factor ◽  
Isotonic Saline ◽  
Control Group ◽  
Peritoneal Fibrosis ◽  
Protein Loss ◽  
Cancer Antigen 125 ◽  
Converting Enzyme Inhibitors ◽  
Plasma Urea ◽  
Peritoneal Function

Objective Peritoneal fibrosis (PF) is one of the most serious causes of failure in continuous ambulatory peritoneal dialysis (PD). Although the underlying mechanism responsible for the genesis of PF is still unknown, transforming growth factor p (TGFβ1) has been shown to be associated with PF. Angiotensin converting enzyme inhibitors have been shown to prevent the stimulating effect of growth factors. The aim of the present study was to investigate the effect of enalapril on peritoneal function and morphology in a rat model of experimental PF. Methods Twenty-one albino Wistar rats were divided into three groups: ( 1 ) the control group (C) received 10 mL isotonic saline intraperitoneally (IP), ( 2 ) the dextrose (Dx) group 10 mL 3.86% dextrose PD solution IP, and ( 3 ) the enalapril-treated group (ENA) 10 cc 3.86% dextrose PD solution IP plus 100 mg/L enalapril in drinking water. After 4 weeks, a 1-hour peritoneal equilibration test was performed with 20 mL 2.27% dextrose PD solution. Dialysate-to-plasma urea ratio (D/P urea), glucose reabsorption (D1/D0 glucose), ultrafiltration (UF) volume, and levels of dialysate protein, TGFβ1, and cancer antigen 125 (CA125) were determined. The parietal peritoneum was evaluated histologically by light microscopy. Results Administration of enalapril resulted in preserved UF (-0.2 ± 0.7 mL vs 1.7 ± 0.3 mL, p < 0.05), protein loss (2.3 ± 0.5 g/L vs 1.6 ± 0.2 g/L, p > 0.05), and peritoneal thickness (77 ± 7 μ vs 38 ± 5 μ, p < 0.001). D/P urea increased significantly in the Dx group ( p < 0.05). Both higher levels of TGFβ1 (undetectable vs 298 ± 43 pg/mL, p < 0.001) and lower levels of CA125 in dialysate effluent (0.94 ± 0.5 U/L vs 0.11 ± 0.1 U/L, p > 0.05) were determined in the Dx group. Conclusion These findings show that peritoneal morphology and function tests were dramatically deranged in the Dx group. The same properties were partially preserved in the ENA group. The production of TGFβ1 was significantly reduced but peritoneal thickness was not completely inhibited. In conclusion, by inhibiting the production of TGFβ1, enalapril can preserve peritoneal histology, peritoneal function, and remodeling of mesothelial cells.

scholarly journals Nephroprotective effect of losartan in IgA model rat

2019 ◽  
Vol 47 (10) ◽  
pp. 5205-5215
Author(s):  
Li Xing ◽  
Er Lin Song ◽  
Xi Bei Jia ◽  
Jing Ma ◽  
Bing Li ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Smooth Muscle Actin ◽  
Control Group ◽  
Model Group ◽  
Sprague Dawley ◽  
Tubulointerstitial Injury ◽  
Expression Levels ◽  
Losartan Group ◽  
Tgf Β1

Objective This study was performed to investigate the possible nephroprotective effects of losartan in a rat model of experimental IgA nephropathy (IgAN). Methods Thirty male Sprague–Dawley rats were randomly divided into three groups. The rats in the model group were treated with bovine serum albumin (oral gavage), lipopolysaccharide (tail vein injection), and carbon tetrachloride (subcutaneous injection); rats in the losartan group received treatments similar to those of the model group, and were orally gavaged with losartan; and rats in the control group received phosphate-buffered saline alone (both orally and intravenously). Results Losartan treatment lowered the 24-hour urinary protein, serum blood urea nitrogen, and serum creatinine levels. Proliferating mesangial cells with a variable increase in the mesangial matrix were detected in the model group, whereas injury in the losartan group was significantly attenuated. Immunohistochemistry revealed that the expression levels of transforming growth factor (TGF)-β1 and α-smooth muscle actin were significantly elevated in the model group but reduced in the losartan group. The expression levels of TGF-β1 and monocyte chemoattractant protein-1 were minimal in the control group, significantly increased in the model group, and reduced in the losartan group. Conclusion Losartan has a protective effect against tubulointerstitial injury in IgAN.

Vitamin D potentiates anti-tumor activity of 5-fluorouracil via modulating caspase-3 and TGF-β1 expression in hepatocellular carcinoma-induced in rats

2018 ◽  
Vol 96 (12) ◽  
pp. 1218-1225 ◽  
Author(s):  
Amal R Ebrahim ◽  
Mohamed El-Mesery ◽  
Amro El-Karef ◽  
Laila A. Eissa
Keyword(s):  
Hepatocellular Carcinoma ◽  
Vitamin D ◽  
Caspase 3 ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Control Group ◽  
Related Factor ◽  
Sprague Dawley ◽  
Gene And Protein Expression ◽  
Tgf Β1

We investigated the role of vitamin D (Vit D) alone and in combination with 5-fluorouracil (5-FU) in thioacetamide (TAA)-induced hepatocellular carcinoma (HCC) in rats. Fifty male Sprague–Dawley rats were randomized into a control group and 4 groups that received TAA (200 mg/kg, i.p.) twice per week for 16 weeks. These 4 groups were further divided as follows: HCC group; 5-FU group (75 mg/kg, i.p., once weekly for 3 weeks starting from the 12th week); Vit D group (200 IU/kg daily by oral tube for 16 weeks); and 5-FU + Vit D group (received the previously mentioned dosage regimens of 5-FU and Vit D). HCC was detected by histopathological changes in liver sections and the elevation of serum α-fetoprotein (AFP). Treatment with 5-FU + Vit D significantly decreased gene expression of nuclear factor erythroid 2-related factor 2 (NrF2) and transforming growth factor β1 (TGF-β1) at both the gene and protein level and serum AFP concentrations in comparison with their corresponding monotherapy. Moreover, 5-FU + Vit D treatment enhanced apoptosis by increasing caspase-3 gene and protein expression. Conclusively, Vit D enhances antitumor activity of 5-FU in an HCC-induced model and improves liver function of treated animals. Combination therapy in a TAA-induced HCC rat model was more effective than 5-FU or Vit D through the modulation of TGF-β1, caspase-3, and NrF2 expressions.

scholarly journals TGF-β1-VEGF-A pathway induces neoangiogenesis with peritoneal fibrosis in patients undergoing peritoneal dialysis

2018 ◽  
Vol 314 (2) ◽  
pp. F167-F180 ◽  
Author(s):  
Tetsuyoshi Kariya ◽  
Hayato Nishimura ◽  
Masashi Mizuno ◽  
Yasuhiro Suzuki ◽  
Yoshihisa Matsukawa ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Growth Factor ◽  
Cell Lines ◽  
Transforming Growth Factor ◽  
Mesothelial Cell ◽  
Mesothelial Cells ◽  
Mrna Levels ◽  
Peritoneal Fibrosis ◽  
Ultrafiltration Failure ◽  
Tgf Β1

The characteristic features of chronic peritoneal injury with peritoneal dialysis (PD) are submesothelial fibrosis and neoangiogenesis. Transforming growth factor (TGF)β and vascular endothelial growth factor (VEGF)-A are the main mediators of fibrosis and neoangiogenesis, respectively; however, the effect of the interaction between them on the peritoneum is not well known. In this study, we investigated the relationship between TGF-β1 and VEGF-A in inducing peritoneal fibrosis by use of human tissues and dialysate, cultured cells, and animal models. The VEGF-A concentration correlated with the dialysate-to-plasma ratio of creatinine (D/P Cr) ( P < 0.001) and TGF-β1 ( P < 0.001) in human PD effluent. VEGF-A mRNA levels increased significantly in the peritoneal tissues of human ultrafiltration failure (UFF) patients and correlated with number of vessels ( P < 0.01) and peritoneal thickness ( P < 0.001). TGF-β1 increased VEGF-A production in human mesothelial cell lines and fibroblast cell lines, and TGF-β1-induced VEGF-A was suppressed by TGF-β receptor I (TGFβR-I) inhibitor. Incremental peak values of VEGF-A mRNA stimulated by TGF-β1 in human cultured mesothelial cells derived from PD patients with a range of peritoneal membrane functions correlated with D/P Cr ( P < 0.05). To evaluate the regulatory mechanisms of VEGF-A and neoangiogenesis in vivo, we administered TGFβR-I inhibitor intraperitoneally in a rat chlorhexidine-induced peritoneal injury (CG) model. TGFβR-I inhibitor administration in the CG model decreased peritoneal thickness ( P < 0.001), the number of vessels ( P < 0.001), and VEGF-A levels ( P < 0.05). These results suggest that neoangiogenesis is associated with fibrosis through the TGF-β1-VEGF-A pathway in mesothelial cells and fibroblasts. These findings are important when considering the strategy for management of UFF in PD patients.

scholarly journals CD133, a Progenitor Cell Marker, is Reduced in Nasal Polyposis and Showed Significant Correlations with TGF-β1 and IL-8

2021 ◽  
Author(s):  
Wagner Vargas Souza Lino ◽  
André Luis Lacerda Bachi ◽  
José Arruda Mendes Neto ◽  
Gabriel Caetani ◽  
Jônatas Bussador do Amaral ◽  
...  
Keyword(s):  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Nasal Polyposis ◽  
Transforming Growth Factor ◽  
Middle Turbinate ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Histologic Analysis ◽  
Aspirin Intolerance ◽  
Tgf Β1

Abstract Introduction Combination of chronic inflammation and an altered tissue remodeling process are involved in the development of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP). Studies demonstrated that mesenchymal stem cells expressing the progenitor gene CD133 were involved in a significant reduction of the chronic inflammatory process in the polypoid tissue. Objective To evaluate the levels of CD133 (Prominin-1) in nasal polypoid tissue and its correlation with interleukin-8 (IL-8) and transforming growth factor β1 (TGF-β1). Methods A total of 74 subjects were divided in the following groups: control group (n = 35); chronic rhinosinusitis with nasal polyps nonpresenting comorbid asthma and aspirin intolerance (CRSwNPnonAI) group (n = 27); and chronic rhinosinusitis with nasal polyps presenting comorbid asthma and aspirin intolerance (CRSwNPAI) group (n = 12). Histologic analysis and also evaluation of the concentration of CD133, IL-8, and TGF-β1 by enzyme-linked immunosorbent assay (ELISA) kits were performed in nasal tissue obtained from nasal polypectomy or from middle turbinate tissue. Results Higher eosinophilic infiltration was found in both CRSwNP groups by histologic analysis. Lower levels of TGF-β1 and IL-8 were observed in both CRSwNP groups when compared with the control group, whereas the CD133 levels were significantly reduced only in the CRSwNPnonAI group compared with the control group. Conclusion It was demonstrated that the nasal mucosa presenting polyposis showed a significant reduction of CD133 levels, and also that this reduction was significantly correlated with the reduction of TGF-β1 levels, but not with IL-8 levels. Therefore, these findings may be involved in the altered inflammatory and remodeling processes observed in the nasal polyposis.

scholarly journals Yiqi Wenyang Fang ameliorates allergic rhinitis through inhibiting inflammatory response and promoting the expression of Foxp3

2016 ◽  
Vol 29 (4) ◽  
pp. 696-706 ◽  
Author(s):  
Jun Shi ◽  
Yu Liu ◽  
Shihai Yan ◽  
Daonan Yan
Keyword(s):  
Allergic Rhinitis ◽  
Inflammatory Response ◽  
Transforming Growth Factor ◽  
Treg Cells ◽  
Pcr Analysis ◽  
Enzyme Linked Immunosorbent Assay ◽  
High Dose ◽  
Sprague Dawley ◽  
Model Control ◽  
Tgf Β1

Allergic rhinitis (AR) is an inflammatory disease with a hypersensitivity response to environmental stimulus. The aim of this study was to evaluate the effect of Yiqi Wenyang Fang (YWF) on AR and investigate the underlying mechanism. A total of 48 female Sprague-Dawley rats were randomly divided into six groups (normal control, model control, YWF at low dose, YWF at median dose, YWF at high dose, and loratadine). Rats were injected with antigen for sensitization. Then, rats in the YWF groups were treated with different dose of YWF for 28 days. Loratadine was used as a positive control. Number of sneezes, degree of runny nose, nasal rubbing movements, and tissue damage were scored. The protein and mRNA expression of Foxp3 were determined by western blot and real time-PCR analysis, respectively. Flow cytometry was used to detect the number of CD4+CD25+Foxp3+ Treg cells. The content of interleukin (IL)-10, transforming growth factor β1 (TGF-β1), IL-13, and IL-4 in the serum were detected by enzyme-linked immunosorbent assay (ELISA). Scores of symptoms were significantly reduced and nasal mucosa damage was alleviated after YWF administration. YWF increased the expression of Foxp3, IL-10, TGF-β1, and number of CD4+CD25+Foxp3+ Treg cells which were reduced by antigen injection. The expression levels of IL-13 and IL-4 were increased after antigen administration while decreased after YWF treatment. YWF may ameliorate AR through inhibiting inflammatory response and promoting Foxp3 expression.

Itraconazole Attenuates Peritoneal Fibrosis Through Its Effect on the Sonic Hedgehog Signaling Pathway in Mice

2018 ◽  
Vol 48 (6) ◽  
pp. 456-464 ◽  
Author(s):  
Jin Sug Kim ◽  
Kyung Sook Cho ◽  
Seon Hwa Park ◽  
Sang Ho Lee ◽  
Ji Hwan Lee ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Sonic Hedgehog ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Isotonic Saline ◽  
Control Group ◽  
Protective Effects ◽  
Peritoneal Fibrosis ◽  
Shh Signaling ◽  
Itraconazole Treatment

Background: Peritoneal fibrosis is a devastating complication of peritoneal dialysis. However, its precise mechanism is unclear, and specific treatments have not yet been established. Recent evidence suggests that the sonic hedgehog (SHH) signaling pathway is involved in tissue fibrogenesis. Drugs that inhibit this pathway are emerging in the field of anti-fibrosis therapy. Itraconazole, an anti-fungal agent, was also recently recognized as an inhibitor of the SHH signaling pathway. In this study, we used a mouse model to investigate whether the SHH signaling pathway is involved in the development of peritoneal fibrosis and the effects of itraconazole on peritoneal fibrosis. Methods: Peritoneal fibrosis was induced by intraperitoneal (IP) injection of 0.1% chlorhexidine gluconate (CG) solution every other day for 4 weeks, with or without itraconazole treatment (20 mg/kg, IP injection on a daily basis). Male C57BL/6 mice were divided into 4 groups: saline group, saline plus itraconazole group, CG group, and CG plus itraconazole group. Isotonic saline was administered intraperitoneally to the control group. The peritoneal tissues were evaluated for histological changes, expression of fibrosis markers, and the main components of the SHH signaling pathway. Results: Peritoneal thickening was evident in the CG group and was significantly decreased by itraconazole administration (80.4 ± 7.7 vs. 28.2 ± 3.8 µm, p < 0.001). The expression of the following SHH signaling pathway components was upregulated in the CG group and suppressed by itraconazole treatment: SHH, patched, smoothened, and glioma-associated oncogene transcription factor 1. The IP injection of CG solution increased the expression of fibrosis markers such as α-smooth muscle actin and transforming growth factor-β1 in the peritoneal tissues. Itraconazole treatment significantly decreased the expression of these markers. Conclusion: Our study provides the first evidence that the SHH signaling pathway may be implicated in peritoneal fibrosis. It also demonstrates that itraconazole treatment has protective effects on peritoneal fibrosis through the regulation of the SHH signaling pathway. These findings suggest that blockage of the SHH signaling pathway is a potential therapeutic strategy for peritoneal fibrosis.

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