scholarly journals Indoxyl Sulfate Induces Mesangial Cell Proliferation via the Induction of COX-2

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Shuzhen Li ◽  
Sijie Cheng ◽  
Zhenzhen Sun ◽  
Harr-keshauve Mungun ◽  
Wei Gong ◽  
...  
Keyword(s):  
Mesangial Cell ◽  
Underlying Mechanism ◽  
Residual Renal Function ◽  
Cell Number ◽  
Indoxyl Sulfate ◽  
Synthesis Rate ◽  
Cycle Phase ◽  
Progressive Loss ◽  
Cox 2 ◽  
Stage Renal Disease

Indoxyl sulfate (IS) is one of important uremic toxins and is markedly accumulated in the circulation of end stage renal disease (ESRD) patients, which might contribute to the damage of residual nephrons and progressive loss of residual renal function (RRF). Thus this study was undertaken to investigate the role of IS in modulating mesangial cell (MC) proliferation and the underlying mechanism. The proliferation of MCs induced by IS was determined by cell number counting, DNA synthase rate, and cell cycle phase analysis. COX-2 expression was examined by Western blotting and qRT-PCR, and a specific COX-2 inhibitor NS398 was applied to define its role in IS-induced MC proliferation. Following IS treatment, MCs exhibited increased total cell number, DNA synthesis rate, and number of cells in S and G2 phases paralleled with the upregulation of cyclin A2 and cyclin D1. Next, we found an inducible inflammation-related enzyme COX-2 was remarkably enhanced by IS, and the inhibition of COX-2 by NS398 significantly blocked IS-induced MC proliferation in line with a blockade of PGE2 production. These findings indicated that IS could induce MC proliferation via a COX-2-mediated mechanism, providing new insights into the understanding and therapies of progressive loss of RRF in ESRD.

scholarly journals mPGES-1-Derived PGE2 Contributes to Indoxyl Sulfate-Induced Mesangial Cell Proliferation

2017 ◽  
Vol 43 (1) ◽  
pp. 271-281
Author(s):  
Shuzhen Li ◽  
Zhenzhen Sun ◽  
Guixia Ding ◽  
Wei Gong ◽  
Jing Yu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Mesangial Cell ◽  
Cell Number ◽  
Pathological Process ◽  
Indoxyl Sulfate ◽  
Prostaglandin E ◽  
Mrna Levels ◽  
Mesangial Cell Proliferation ◽  
Cox 2

Background/Aims: We previously reported that indoxyl sulfate (IS) could cause mesangial cell (MC) proliferation via a cyclooxygenase (COX)-2-dependent mechanism. However, the specific prostaglandin contributing to COX-2 effect on IS-induced MC proliferation remained unknown. Thus, the present study was undertaken to examine the role of microsomal prostaglandin E synthase-1 (mPGES-1)-derived Prostaglandin E2 (PGE2) in IS-induced MC proliferation. Methods: IS was administered to the MCs with or without mPGES-1 siRNA pretreatment to induce the MC proliferation which was determined by cell cycle analysis, DNA synthesis, and the expressions of cyclins. In another experimental setting, PGE2 was applied to the MCs to examine its direct effect on MC proliferation, as well as the regulation of prostaglandin E receptors (EPs) by qRT-PCR. Results: With the administration of IS, mPGES-1(not mPGES-2 and cytosolic PGES) was significantly upregulated at both protein and mRNA levels in line with a promoted MC proliferation. Interestingly, silencing mPGES-1 reduced cell number in S and G2 phases and blocked the upregulation of cyclin A2 and cyclin D1 in parallel with blunted PGE2 release after IS treatment, indicating that mPGES-1-derived PGE2 could contribute to MC proliferation. Furthermore, we confirmed that exogenous PGE2 could directly trigger the proliferative response in MCs. Lastly, we observed a selective upregulation of EP2 after PGE2 treatment and enhanced phosphorylation of NF-κB following IS administration in MCs, suggesting the potential involvements of EP2 and NF-κB in this pathological process. Conclusion: mPGES-1-derived PGE2 contributed to IS-induced mesangial cell proliferation.

scholarly journals Improved response of human gingival fibroblasts to titanium coated with micro-/nano-structured tantalum

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Chu-nan Zhang ◽  
Lin-yi Zhou ◽  
Shu-jiao Qian ◽  
Ying-xin Gu ◽  
Jun-yu Shi ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Underlying Mechanism ◽  
Cell Number ◽  
Human Gingival Fibroblasts ◽  
Superior Performance ◽  
Control Group ◽  
Human Gingival Fibroblast ◽  
Gingival Fibroblast ◽  
Gingival Fibroblasts ◽  
Integrin Β1

Abstract Objectives This study aims to evaluate the ability of tantalum-coated titanium to improve human gingival fibroblasts’ adhesion, viability, proliferation, migration performance, and the potential molecular mechanisms. Materials and methods Titanium plates were divided into two groups: (1) no coating (Ti, control), (2) Tantalum-coated titanium (Ta-coated Ti). All samples were characterized by scanning electronic microscopy, surface roughness, and hydrophilicity. Fibroblasts’ performance were analyzed by attached cell number at 1 h, 4 h, and 24 h, morphology at 1 h and 4 h, viability at 1 day, 3 days, 5 days, and 7 days, recovery after wounding at 6 h, 12 h, and 24 h. RT-PCR, western blot were applied to detect attachment-related genes’ expression and protein synthesis at 4 h and 24 h. Student’s t test was used for statistical analysis. Results Tantalum-coated titanium demonstrates a layer of homogeneously distributed nano-grains with mean diameter of 25.98 (± 14.75) nm. It was found that after tantalum deposition, human gingival fibroblasts (HGFs) adhesion, viability, proliferation, and migration were promoted in comparison to the control group. An upregulated level of Integrin β1 and FAK signaling was also detected, which might be the underlying mechanism. Conclusion In the present study, adhesion, viability, proliferation, migration of human gingival fibroblasts are promoted on tantalum-coated titanium, upregulated integrin β1 and FAK might contribute to its superior performance, indicating tantalum coating can be applied in transmucosal part of dental implant. Clinical significance Tantalum deposition on titanium surfaces can promote human gingival fibroblast adhesion, accordingly forming a well-organized soft tissue sealing and may contribute to a successful osseointegration.

Hypoxia and high glucose cause exaggerated mesangial cell growth and collagen synthesis: role of osteopontin

2001 ◽  
Vol 280 (4) ◽  
pp. F667-F674 ◽  
Author(s):  
Chhinder P. Sodhi ◽  
Sarojini A. Phadke ◽  
Daniel Batlle ◽  
Atul Sahai
Keyword(s):  
Cell Growth ◽  
High Glucose ◽  
Collagen Synthesis ◽  
Type Iv Collagen ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Neutralizing Antibody ◽  
Cell Number ◽  
Mrna Levels ◽  
Type Iv

The effect of hypoxia on the proliferation and collagen synthesis of cultured rat mesangial cells was examined under normal-glucose (NG, 5 mM) and high-glucose (HG, 25 mM)-media conditions. In addition, a role for osteopontin (OPN) in mediating these processes was assessed. Quiescent cultures were exposed to hypoxia (3% O2) and normoxia (18% O2) in a serum-free medium with NG or HG, and cell proliferation, collagen synthesis, and OPN expression were assessed. Cells exposed to hypoxia in NG medium resulted in significant increases in [3H]thymidine incorporation, cell number, and [3H]proline incorporation, respectively. HG incubations also produced significant stimulation of these parameters under normoxic conditions, which were markedly enhanced in cells exposed to hypoxia in HG medium. In addition, hypoxia and HG stimulated the mRNA levels of type IV collagen, and the combination of hypoxia and HG resulted in additive increases in type IV collagen expression. Hypoxia and HG also stimulated OPN mRNA and protein levels in an additive fashion. A neutralizing antibody to OPN or its β3-integrin receptor significantly blocked the effect of hypoxia and HG on proliferation and collagen synthesis. In conclusion, these results demonstrate for the first time that hypoxia in HG medium produces exaggerated mesangial cell growth and type IV collagen synthesis. In addition, OPN appears to play a role in mediating the accelerated mesangial cell growth and collagen synthesis found in a hyperglycemic and hypoxic environment.

scholarly journals Anti-inflammatory properties of Amomum maximum Roxb and Amomum muricarpum Elmer in the North of Vietnam

2021 ◽  
Vol 19 (2) ◽  
pp. 301-307
Author(s):  
Pham Anh Thu ◽  
Nguyen Hoang Son ◽  
Le Thanh Huong ◽  
Nguyen Hai Dang
Keyword(s):  
Nitric Oxide ◽  
Defense Mechanism ◽  
Cell Model ◽  
Underlying Mechanism ◽  
Gastrointestinal Diseases ◽  
The North ◽  
Ic50 Values ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Low Cytotoxicity

Inflammation is the body's homeostatic defense mechanism in which the immune system reacts to remove foreign bodies. Chronic inflammation can increase the risk for additional damage like autoimmune diseases, arthritis, diabetes and can result in death. Amomum maximum Roxb and Amomum muricarpum Elmer distributed widely in Vietnam have been used in traditional medicine for treatment of some gastrointestinal diseases. This study aimed to investigate the anti-inflammatory effects of the methanol extracts of A. maximum (AMM) and A. muricarpum Elmer (AMC) in murine macrophage RAW 264.7 cell line. The total extracts showed that the extracts exhibited low cytotoxicity and potent anti-inflammatory activities by suppressing excessive nitric oxide (NO). The IC50 values of AMC and AMM were found to be 12.67 ± 1.7 µg/mL and 42.7 ± 2.5 µg/mL, respectively. To elucidate the underlying mechanism, the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were evaluated using Western blot analysis. Our data demonstrated that AMC reduced the inflammatory response in a lipopolysaccharide (LPS)-induced RAW264.7 cell model via inhibition of iNOS and COX-2 while AMM seemed to modulate the inflammatory effect through the iNOS pathway only. In conclusion, AMM and AMC root extracts might be potential candidates for a study of naturally alternative anti-inflammatory drugs.

scholarly journals Biological basis of hypoalbuminemia in ESRD.

1998 ◽  
Vol 9 (12) ◽  
pp. 2368-2376 ◽  
Author(s):  
G A Kaysen
Keyword(s):  
Peritoneal Dialysis ◽  
Acute Phase ◽  
Synthesis Rate ◽  
Albumin Concentration ◽  
Albumin Synthesis ◽  
Dialysis Patients ◽  
Extravascular Space ◽  
Amyloid A ◽  
Stage Renal Disease ◽  
End Stage

Hypoalbuminemia is associated with mortality in patients with end-stage renal disease (ESRD) maintained either on peritoneal dialysis (PD) or hemodialysis (HD). Serum albumin concentration is determined by its rate of synthesis, by the catabolic rate constant (the fraction of the vascular pool catabolized per unit time), by external losses, and by redistribution from the vascular to the extravascular space. Hypoalbuminemia in dialysis patients is primarily a consequence of reduced albumin synthesis rate in both HD and PD patients, and in the case of PD patents, of transperitoneal albumin losses as well. Continuous ambulatory peritoneal dialysis patients are able to increase albumin synthesis to replace losses. Thus, ESRD does not directly suppress albumin synthesis. The rate of albumin synthesis is inversely proportional to the serum concentration of one potential acute phase protein (alpha2 macroglobulin), and albumin concentration is inversely proportional to that of either C-reactive protein or serum amyloid A in both HD and PD patients. The cause of decreased albumin synthesis is primarily a response to inflammation (the acute phase response), although it is possible that inadequate nutrition may also contribute. The cause of the inflammatory response is not immediately evident. There is no evidence that shifts of albumin to the extravascular space or that dilution of the plasma by volume expansion plays any role in causing hypoalbuminemia in ESRD patients.

scholarly journals Antitumor activity of L-asparaginase from Erwinia Carotovora from against different leukemic and solid tumours cell lines

2013 ◽  
Vol 59 (5) ◽  
pp. 498-513 ◽  
Author(s):  
O.Yu. Abakumova ◽  
O.V. Podobed ◽  
P.A. Karalkin ◽  
L.I. Kondakova ◽  
N.N. Sokolov
Keyword(s):  
Dna Synthesis ◽  
Tumor Cells ◽  
Solid Tumor ◽  
Human Fibroblasts ◽  
Erwinia Carotovora ◽  
Cell Number ◽  
Jurkat Cells ◽  
Leukemic Cells ◽  
Cycle Phase ◽  
Tumor Cell Death

We have studied dose- and time-dependent antitumor and cytotoxic effects of Erwinia carotovora L-asparaginase (ECAR LANS) and Escherichia coli L-asparaginase (MEDAC) on human leukemic cells and human and animal solid tumor cells. We determined the sensitivity of tumor cells to L-asparaginases, as well the effect L-asparaginases on cell growth rate, protein and DNA synthesis per se and with addition of different cytostatics. The data obtained demonstrated that ECAR LANS L-asparaginase suppressed growth of all tested solid tumor cells. Evaluation of leukemic cell number after treatment with L-asparaginases for 24, 48 and 72 h demonstrated that asparagine deficiency did not kill cells but stopped normal cell division and had no effect on protein and DNA synthesis. Cytofluorometric study of solid and leukemic cells demonstrated that the treatment with L-asparaginase for 72 h did not change cell cycle phase distribution and did not increase the number of apoptotic cells. The HL-60 cell line was only exemption. At the same time, cells treatment with L-asparaginase and doxorubicin combination leaded to increase of apoptotypical cell number to 60% for MCF7 cells, to 40% for Jurkat cells and to 99% for HL-60 cells. We have excluded apoptosis as main reason for tumor cell death after asparaginase treatment because multi resistant Jurkat/A4 cells have been asparaginase sensitive. We have not found ECAR LANS L-asparaginase effect on normal human fibroblasts growth ability and we had come to conclusion that enzyme cytotoxcisity related only with asparagine deficiency.

scholarly journals Reversible glomerular hypertrophy in adult patients with primary focal segmental glomerulosclerosis.

1997 ◽  
Vol 8 (11) ◽  
pp. 1668-1678
Author(s):  
K Nishimoto ◽  
H Shiiki ◽  
T Nishino ◽  
H Uyama ◽  
M Iwano ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Focal Segmental Glomerulosclerosis ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Cell Number ◽  
Glomerular Hypertrophy ◽  
Control Subjects ◽  
Segmental Glomerulosclerosis ◽  
The Mean ◽  
Glomerular Tuft

The present study was performed to assess the pathogenetic role of glomerular hypertrophy in patients with primary focal segmental glomerulosclerosis (FSGS). We studied 14 patients with FSGS by morphometry. In seven patients, minimal change nephrotic syndrome (MCNS) was diagnosed on the first renal biopsy, but FSGS was diagnosed on the second biopsy (MCNS-FSGS group). Seven other patients with FSGS on the first biopsy underwent second biopsies while in remission (FSGS-R group). Biopsy results were compared with biopsies from 10 patients with MCNS and seven control subjects. Nonsclerotic glomeruli were examined. The mean glomerular tuft area, whole glomerular area, and number of mesangial cells were significantly increased in both biopsies from the MCNS-FSGS group and in the first biopsies obtained during the nephrotic stage of the FSGS-R group, compared with control subjects and patients with MCNS. Biopsies from FSGS patients in remission showed that the mean glomerular tuft area and number of mesangial cells were significantly decreased. The fractional extracellular matrix area (extracellular matrix area/glomerular tuft area) and mesangial cell density (mesangial cell number/glomerular tuft area) in FSGS during both nephrotic and remission stages were the same as those in control subjects and patients with MCNS. The present study suggests that glomerular hypertrophy precedes the development of glomerulosclerosis in FSGS and is reversible when patients are in remission. These features support the pathogenetic importance of glomerular hypertrophy in patients with primary FSGS.

scholarly journals Periodontal Disease in Patients Receiving Dialysis

2019 ◽  
Vol 20 (15) ◽  
pp. 3805
Author(s):  
Yasuyoshi Miyata ◽  
Yoko Obata ◽  
Yasushi Mochizuki ◽  
Mineaki Kitamura ◽  
Kensuke Mitsunari ◽  
...  
Keyword(s):  
Renal Replacement Therapy ◽  
Periodontal Disease ◽  
Replacement Therapy ◽  
Healthy Individuals ◽  
Progressive Loss ◽  
Medical Instruments ◽  
Stage Renal Disease ◽  
End Stage ◽  
The Impact

Chronic kidney disease (CKD) is characterized by kidney damage with proteinuria, hematuria, and progressive loss of kidney function. The final stage of CKD is known as end-stage renal disease, which usually indicates that approximately 90% of normal renal function is lost, and necessitates renal replacement therapy for survival. The most widespread renal replacement therapy is dialysis, which includes peritoneal dialysis (PD) and hemodialysis (HD). However, despite the development of novel medical instruments and agents, both dialysis procedures have complications and disadvantages, such as cardiovascular disease due to excessive blood fluid and infections caused by impaired immunity. Periodontal disease is chronic inflammation induced by various pathogens and its frequency and severity in patients undergoing dialysis are higher compared to those in healthy individuals. Therefore, several investigators have paid special attention to the impact of periodontal disease on inflammation-, nutrient-, and bone metabolism-related markers; the immune system; and complications in patients undergoing dialysis. Furthermore, the influence of diabetes on the prevalence and severity of manifestations of periodontal disease, and the properties of saliva in HD patients with periodontitis have been reported. Conversely, there are few reviews discussing periodontal disease in patients with dialysis. In this review, we discuss the available studies and review the pathological roles and clinical significance of periodontal disease in patients receiving PD or HD. In addition, this review underlines the importance of oral health and adequate periodontal treatment to maintain quality of life and prolong survival in these patients.

Clinical Utility of Potassium-Sparing Diuretics to Maintain Normal Serum Potassium in Peritoneal Dialysis Patients

2017 ◽  
Vol 37 (1) ◽  
pp. 63-69 ◽  
Author(s):  
Tibor Fülöp ◽  
Lajos Zsom ◽  
Betzaida Rodríguez ◽  
Sabahat Afshan ◽  
Jamie V. Davidson ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Serum Potassium ◽  
Residual Renal Function ◽  
Normal Serum ◽  
Dialysis Adequacy ◽  
Cross Sectional ◽  
Laboratory Variables ◽  
Stage Renal Disease ◽  
End Stage ◽  
Vexing Problem

BackgroundHypokalemia is a vexing problem in end-stage renal disease patients on peritoneal dialysis (PD), and oral potassium supplements (OPS) have limited palatability. Potassium-sparing diuretics (KSD) (spironolactone, amiloride) may be effective in these patients.MethodsWe performed a cross-sectional review of 75 current or past (vintage > 6 months) PD patients with regard to serum potassium (K+), OPS, and KSD utilization. We reviewed charts for multiple clinical and laboratory variables, including dialysis adequacy, residual renal function, nutritional status and co-existing medical therapy.ResultsThe cohort was middle-aged with a mean age of 49.2 years (standard deviation [SD] = 14.7) and overweight with a body mass index of 29.5 (6.7) kg/m2. Of all the participants, 57.3% were female, 73.3% African-American, and 48% diabetic with an overall PD vintage of 28.2 (24.3) months at the time of enrollment. Weekly Kt/V was 2.12 (0.43), creatinine clearance was 73.5 (33.6) L/week/1.73 m2with total daily exchange volume of 10.8 (2.7) L. Residual urine output (RUO) measured at 440 (494) mL (anuric 30.6%). Three-month averaged serum K+measured at 4 (0.5) mmol/L with 36% of the participants receiving K+supplements (median: 20 [0;20] mmol/day) and 41.3% KSD (spironolactone dose: 25 – 200 mg/day; amiloride dose: 5 – 10 mg/day). Serum K+correlated positively with weekly Kt/V (r = 0.239; p = 0.039), PD vintage (r = 0.272; p = 0.018) but not with PD modality, daily exchange volume, RUO, or KSD use. However, KSD use was associated with decreased use of OPS (r = -0.646; p < 0.0001).ConclusionsPotassium-sparing diuretics were effective in this cohort of PD patients and decreased the need for OPS utilization.

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