scholarly journals Cytoprotective Effect of Liposomal Puerarin on High Glucose-Induced Injury in Rat Mesangial Cells

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1177
Author(s):  
Lassina Barro ◽  
Jui-Ting Hsiao ◽  
Chu-Yin Chen ◽  
Yu-Lung Chang ◽  
Ming-Fa Hsieh
Keyword(s):  
Protective Effect ◽  
Transforming Growth Factor Beta ◽  
High Glucose ◽  
High Performance ◽  
Transforming Growth Factor ◽  
Nuclear Translocation ◽  
Mesangial Cells ◽  
Diabetic Patients ◽  
Pueraria Lobata ◽  
Cytoprotective Effect

In diabetic patients, high glucose and high oxidative states activate gene expression of transforming growth factor beta (TGF-β) and further translocate Smad proteins into the nucleus of renal cells. This signal pathway is characterized as the onset of diabetic nephropathy. Puerarin is an active ingredient extracted from Pueraria lobata as an anti-hyperglycemic and anti-oxidative agent. However, the poor oral availability and aqueous solubility limit its pharmaceutical applications. The present paper reports the liposomal puerarin and its protective effect on high glucose-injured rat mesangial cells (RMCs). The purity of puerarin extracted from the root of plant Pueraria lobata was 83.4% as determined by the high-performance liquid chromatography (HPLC) method. The liposomal puerarin was fabricated by membrane hydration followed by ultrasound dispersion and membrane extrusion (pore size of 200 nm). The fabricated liposomes were examined for the loading efficiency and contents of puerarin, the particle characterizations, the radical scavenge and the protective effect in rat mesangial cells, respectively. When the liposomes were subjected to 20 times of membrane extrusion, the particle size of liposomal puerarin can be reduced to less than 200 nm. When liposomal puerarin in RMCs in high glucose concentration (33 mM) was administered, the over-expression of TGF-β and the nuclear translocation of Smad 2/3 proteins was both inhibited. Therefore, this study successfully prepared the liposomal puerarin and showed the cytoprotective effect in RMCs under high glucose condition.

scholarly journals Microparticles as Potential Mediators of High Glucose-Induced Renal Cell Injury

Biomolecules ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. 348 ◽  
Author(s):  
Ravindran ◽  
Pasha ◽  
Agouni ◽  
Munusamy
Keyword(s):  
Er Stress ◽  
Signaling Pathways ◽  
Transforming Growth Factor Beta ◽  
High Glucose ◽  
Cell Injury ◽  
Transforming Growth Factor ◽  
Nuclear Translocation ◽  
Epithelial Mesenchymal Transition ◽  
Smooth Muscle Actin ◽  
Mesenchymal Transition

Diabetic nephropathy (DN) is the most common cause of chronic kidney disease worldwide. Activation of signaling pathways such as the mammalian target of rapamycin (mTOR), extracellular signal-regulated kinases (ERK), endoplasmic reticulum (ER) stress, transforming growth factor-beta (TGF-β), and epithelial-mesenchymal transition (EMT), are thought to play a significant role in the etiology of DN. Microparticles (MPs), the small membrane vesicles containing bioactive signals shed by cells upon activation or during apoptosis, are elevated in diabetes and were identified as biomarkers in DN. However, their exact role in the pathophysiology of DN remains unclear. Here, we examined the effect of MPs shed from renal proximal tubular cells (RPTCs) exposed to high glucose conditions on naïve RPTCs in vitro. Our results showed significant increases in the levels of phosphorylated forms of 4E-binding protein 1 and ERK1/2 (the downstream targets of mTOR and ERK pathways), phosphorylated-eIF2α (an ER stress marker), alpha smooth muscle actin (an EMT marker), and phosphorylated-SMAD2 and nuclear translocation of SMAD4 (markers of TGF-β signaling). Together, our findings indicate that MPs activate key signaling pathways in RPTCs under high glucose conditions. Pharmacological interventions to inhibit shedding of MPs from RPTCs might serve as an effective strategy to prevent the progression of DN.

scholarly journals BKCa Mediates Dysfunction in High Glucose Induced Mesangial Cell Injury via TGF-β1/Smad2/3 Signaling Pathways

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Zhigui Wu ◽  
Wenxian Yin ◽  
Mengqi Sun ◽  
Yuankai Si ◽  
Xiaoxiao Wu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Kidney Disease ◽  
Signaling Pathways ◽  
Transforming Growth Factor Beta ◽  
High Glucose ◽  
Diabetic Kidney Disease ◽  
Transforming Growth Factor ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Diabetic Kidney

Objective. To explore the role and mechanism of BKCa in diabetic kidney disease. Methods. Rat mesangial cells (MCs) HBZY-1 were cultured with high glucose to simulate the high-glucose environment of diabetic kidney disease in vivo. The effects of large conductance calcium-activated potassium channel (BKCa) on proliferation, migration, and apoptosis of HBZY-1 cells were observed. The contents of transforming growth factor beta 1 (TGF-β1), Smad2/3, collagen IV (Col IV), and fibronectin (FN) in the extracellular matrix were also observed. Results. High glucose significantly damaged HBZY-1 cells, which enhanced the ability of cell proliferation, migration, and apoptosis, and increased the secretion of Col IV and FN. Inhibition of BKCa and TGF-β1/Smad2/3 signaling pathways can inhibit the proliferation, migration, and apoptosis of HBZY-1 cells and suppress the secretion of Col IV and FN. The effect of excitation is the opposite. Conclusions. BKCa regulates mesangial cell proliferation, migration, apoptosis, and secretion of Col IV and FN and is associated with TGF-β1/Smad2/3 signaling pathway.

High glucose stimulates expression of p27Kip1 in cultured mouse mesangial cells: relationship to hypertrophy

1997 ◽  
Vol 273 (3) ◽  
pp. F348-F356 ◽  
Author(s):  
G. Wolf ◽  
R. Schroeder ◽  
F. N. Ziyadeh ◽  
F. Thaiss ◽  
G. Zahner ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
High Glucose ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
G1 Phase ◽  
Glucose Medium ◽  
Cyclin Dependent Kinases ◽  
P27kip1 Protein ◽  
High Glucose Medium ◽  
First Time

Hypertrophy of mesangial cells is an early hallmark of diabetic nephropathy. We have previously shown that murine mesangial cells (MMC), cultured in high-glucose medium, are arrested in the G1 phase of the cell cycle and undergo hypertrophy. This study was undertaken to test whether high glucose-containing medium influences the expression of p27Kip1, an inhibitor of G1 phase active cyclin-dependent kinases (CDK). Incubation of MMC, in the absence of other factors for 48-96 h, in medium containing high D-glucose (450 mg/dl), stimulated p27Kip1 protein expression but failed to influence mRNA abundance. These effects were independent of the osmolarity of the medium. High glucose-stimulated expression of p27Kip1 involved activation of protein kinase C and was partly dependent on induction of transforming growth factor-beta (TGF-beta). Immunoprecipitation experiments revealed that only small amounts of p27Kip1 protein from MMC grown in high-glucose medium preferentially associates with CDK2 but not with CDK4. The p27Kip1 antisense, but not missense, oligonucleotides inhibited high glucose-stimulated total protein synthesis and facilitated G1 phase exit. Our data showed for the first time that expression of p27Kip1 protein is pivotal in mesangial cell hypertrophy induced by high ambient glucose. These findings may be important in the deciphering of molecular processes causing diabetic glomerular hypertrophy.

High glucose activates PKC-ζ and NADPH oxidase through autocrine TGF-β1 signaling in mesangial cells

2008 ◽  
Vol 295 (6) ◽  
pp. F1705-F1714 ◽  
Author(s):  
Ling Xia ◽  
Hong Wang ◽  
Snezana Munk ◽  
Janice Kwan ◽  
Howard J. Goldberg ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
High Glucose ◽  
Transforming Growth Factor ◽  
Nuclear Translocation ◽  
Kinase Inhibitor ◽  
Mesangial Cells ◽  
Pi3 Kinase ◽  
Kinase Assay ◽  
Ros Generation ◽  
Pkc Ζ

Conversion of normally quiescent mesangial cells into extracellular matrix-overproducing myofibroblasts in response to high ambient glucose and transforming growth factor (TGF)-β1 is central to the pathogenesis of diabetic nephropathy. Previously, we reported that mesangial cells respond to high glucose by generating reactive oxygen species (ROS) from NADPH oxidase dependent on protein kinase C (PKC) -ζ activation. We investigated the role of TGF-β1 in this action of high glucose on primary rat mesangial cells within 1–48 h. Both high glucose and exogenous TGF-β1 stimulated PKC-ζ kinase activity, as measured by an immune complex kinase assay and immunofluorescence confocal cellular imaging. In high glucose, Akt Ser473 phosphorylation appeared within 1 h and Smad2/3 nuclear translocation was prevented with neutralizing TGF-β1 antibodies. Neutralizing TGF-β1 antibodies, or a TGF-β receptor kinase inhibitor (LY364947), or a phosphatidylinositol 3,4,5-trisphosphate (PI3) kinase inhibitor (wortmannin), prevented PKC-ζ activation by high glucose. TGF-β1 also stimulated cellular membrane translocation of PKC-α, -β1, -δ, and -ε, similar to high glucose. High glucose and TGF-β1 enhanced ROS generation by mesangial cell NADPH oxidase, as detected by 2,7-dichlorofluorescein immunofluorescence. This response was abrogated by neutralizing TGF-β1 antibodies, LY364947, or a specific PKC-ζ pseudosubstrate peptide inhibitor. Expression of constitutively active PKC-ζ in normal glucose caused upregulation of p22phox, a likely mechanism of NADPH oxidase activation. We conclude that very early responses of mesangial cells to high glucose include autocrine TGF-β1 stimulation of PKC isozymes including PI3 kinase activation of PKC-ζ and consequent generation of ROS by NADPH oxidase.

Gastrodin protects against high glucose-induced cardiomyocyte toxicity via GSK-3β-mediated nuclear translocation of Nrf2

2021 ◽  
pp. 096032712110028
Author(s):  
Z Dong ◽  
L Bian ◽  
Y-L Wang ◽  
L-M Sun
Keyword(s):  
Protective Effect ◽  
High Glucose ◽  
Nuclear Translocation ◽  
Glycogen Synthase ◽  
Chinese Herb ◽  
Diabetic Patients ◽  
Dependent Manner ◽  
Rat Cardiomyocytes ◽  
Mortality And Morbidity ◽  
Gsk 3Β

Diabetic cardiomyopathy (DCM) is one of the major complications of diabetes that causes mortality and morbidity in diabetic patients. Gastrodin (GSTD) is a bioactive phenolic glucoside component of an ancient Chinese herb Tianma (Gastrodia elata Bl.), which is widely used for cardiovascular and cerebrovascular diseases by ancient Chinese. Up to now, whether GSTD has a beneficial effect on DCM is unclear. Therefore, this study aimed to investigate the effect of GSTD on high glucose-induced injury in H9c2 rat cardiomyocytes and HL-1 mouse cardiomyocytes, and its underlying mechanisms. High glucose (33 mM) treatment caused cardiomyocyte toxicity, oxidative stress and apoptosis in both H9c2 and HL-1 cells. Under both normal (5.5 mM glucose) and high glucose conditions, GSTD showed protective effect against high glucose-induced cytotoxicity and promoted the nuclear translocation of Nrf2 in a concentration and time-dependent manner in H9c2 and HL-1 cells. Knockdown of Nrf2 expression using siRNA specifically targeting Nrf2 attenuated the protective effect of GSTD. Furthermore, GSTD promoted the nuclear translocation of Nrf2 via activating glycogen synthase kinse-3β (GSK-3β) signaling pathway. 4-benzyl, 2-methyl, 1, 2, 4-thiadiazolidine, 3, 5 dione (TDZD-8), an inhibitor of GSK-3β, inhibited the nuclear translocation of Nrf2 induced by GSTD, and attenuated the protective effect of GSTD as Nrf2 knockdown did. In summary, GSTD could protect against high glucose-induced cardiomyocyte toxicity via GSK-3β-mediated nuclear translocation of Nrf2.

scholarly journals Captopril reverses high-glucose-induced growth effects on LLC-PK1 cells partly by decreasing transforming growth factor-beta receptor protein expressions.

1996 ◽  
Vol 7 (8) ◽  
pp. 1207-1215 ◽  
Author(s):  
J Y Guh ◽  
M L Yang ◽  
Y L Yang ◽  
C C Chang ◽  
L Y Chuang
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
High Glucose ◽  
Transforming Growth Factor ◽  
Receptor Protein ◽  
Tgf Beta ◽  
Beta Receptor ◽  
Protein Expressions ◽  
Beta Receptors ◽  
Growth Factor Beta

Transforming growth factor beta (TGF-beta) may be important in the pathogenesis of diabetic nephropathy, and captopril is effective in treating this disorder. However, the mechanisms of this therapeutic effect as related to TGF-beta and its receptors are not known. Thus, the effects of captopril on cellular growth, TGF-beta 1, and TGF-beta receptors were studied in LLC-PK1 cells cultured in normal (11 mM) or high glucose (27.5 mM). This study found that glucose dose-dependently inhibited cellular mitogenesis while inducing hypertrophy in these cells at 72 h of culture, concomitantly with enhanced TGF-beta 1 messenger RNA (mRNA) and TGF-beta receptor Types I and II protein expressions. Captopril dose-dependently (0.1 to 10 mM) increased cellular mitogenesis and inhibited hypertrophy in these cells. Moreover, captopril also decreased TGF-beta receptor Types I and II protein expressions dose-dependently. However, TGF-beta 1 mRNA was not affected by captopril. It was concluded that high glucose decreased cellular mitogenesis while increasing hypertrophy concomitantly with increased TGF-beta 1 mRNA and TGF-beta receptors in LLC-PK1 cells. Captopril can reverse high-glucose-induced growth effects by decreasing TGF-beta receptor protein expressions.

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