• Korean Journal of Veterinary Research
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• v.44 no.4
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• pp.497-505
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• 2004

The proliferation of mesangial cells has been associated with the development of diabetic nephropathy. The cell proliferation has been regulated by diverse growth factors. Among them, insulin like growth factors(IGFs) are also involved in the pathogenesis of diabetic nephropathy. However, it is not yet known about the effect of high glucose on IGF-I and IGF-II secretion and the relationship between high glucose-induced secretion of IGFs and PKC or oxidative stress in the mesangial cells. Thus, we examined the mechanisms by which high glucose regulates secretion of IGFs in mesangial cells. High glucose(25 mM) increased IGF-I and IGF-II secretion. High glucose-induced increase of IGF-I and IGF-II secretion were blocked by taurine($2{\times}10^{-3}$ M), N-acetyl cystein(NAC, $10^{-5}M$), or GSH($10^{-5}M$) (antioxidants), suggesting the role of oxidative stress. High glucose-induced secretion of IGF-I and IGF-II were blocked by H-7, staurosporine, and bisindolylmaleimide I(protein kinase C inhibitors). On the other hand, high glucose also increased lipid peroxide (LPO) formation in a dose dependent manner. In addition, high glucoseinduced stimulation of LPO formation was blocked by PKC inhibitors. These results suggest that PKC is responsible for the increase of oxidative stress in the action of high glucose-induced secretion of IGF-I and IGF-II in mesangial cells. In conclusion, high glucose stimulates IGF-I and IGF-II secretion via PKCoxidative stress signal pathways in mesangial cells.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.6
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• pp.485-489
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• 2015

Diabetic nephropathy (DN) is the leading cause of end-stage failure of the kidney, but the efficacy of currently available strategies for the prevention of DN remains unsatisfactory. In this study, we investigated the effects of free anthraquinones (FARs) extract, which was extracted from the rhubarb and purified by macroporous resin DM130 with gradient mixtures of ethanol/water as the lelution solvents, in high glucose-cultured glomerular mesangial cells (MCs). The cell proliferation was determined by CCK-8 assay, the levels of TGF-${\beta}1$, CTGF, ColIV and FN proteins in the supernatant of MCs were measured by ELISA assays, and the mRNA levels of these four genes were detected by RT-PCR. The results showed that the increased proliferation of MCs, the mRNA levels and protein expression of TGF-${\beta}1$, CTGF, ColIV and FN induced by high glucose were inhibited after the treatment with the FARs extract. This indicated that FARs extract could inhibit cell proliferation and the expression of main extracellular matrix induced by high glucose in MCs. The FARs extract exhibited potential values for prophylaxis and therapy of DN.

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.4
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• pp.145-148
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• 2007

Gynura procumbens (Lour.) Merr. has been used in some parts of Southeast Asia as a folk medicine to treat kidney diseases, diabetes mellitus, and hyperlipidemia. The present work was undertaken to prove the mechanisms of G. procumbens in the management of glomerular diseases. We investigated the effect of an aqueous extract of G. procumbens on cell proliferation, DNA synthesis, and the expressions of $TGF-{\beta}1$, PDGF-BB, CDK1, CDK2, and CDK4 in fetal bovine serum-activated human mesangial cells (MCs). The G. procumbens extract inhibited proliferation, DNA synthesis, expressions of PDGF-BB, CDK1, and CDK2 mRNA, and expression of $TGF-{\beta}1$ protein in MCs. The inhibitory effect of G. procumbens on MC proliferation may be mediated by suppression of PDGF-BB and $TGF-{\beta}1$ expressions and the modulation of CDK1 and CDK2 expression. Therefore, G. procumbens shows promise as an adjunct therapy in preventing progressive renal diseases.

• The Korea Journal of Herbology
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• v.31 no.5
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• pp.71-78
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• 2016

Objectives : Diabetic nephropathy is one of the most common chronic complications of diabetes and a leading cause of end-stage renal failure in the world. Mesangial cell proliferation is known as the major pathologic features such as glomerulosclerosis and renal fibrosis. Wiryeongtang (WRT) is a well-known traditional herbal formula as therapeutic agents for chronic edema and dysuresia of renal homeostasis. In the present study, we investigated whether WRT inhibits high glucose (HG)-induced renal dysfunction by TGF-β/Smads signal regulation in cultured mesangial cells.Methods : Inhibitory effect of WRT (10-50 ㎍/ml) on HG-stimulated mesangial cells proliferation and dysfunction were evaluated by [³H]-thymidine incorporation, Western blot, and RT-qPCR.Results : WRT significantly decreased HG-accelerated thymidine incorporation in human renal mesangial cell in a dose-dependent levels. WRT induced down-regulation of cyclins/CDKs and up-regulation of CDK inhibitor, p21waf1/cip1 and p27kip1 expression. In addition, HG enhanced expression of dysfunction biomarker such as collagen IV and CTGF, which was markedly attenuated by WRT. WRT decreased TGF-β1 and Smad-2/Smad-4 expression, whereas increased Smad-7 expression under HG. Furthermore, WRT inhibited HG-induced inflammatory factors level such as ICAM-1 and MCP-1 as well as NF-κB p65 nuclear translocation and intracellular ROS production.Conclusions : These results suggested that WRT may alleviate mesangial proliferation and inflammation possibly involved in renal fibrotic process, further diabetic nephropathy through disturbing TGF-β1/Smad signaling and NF-κB/ROS pathway. Thus, WRT might prove to be effective in the treatment of renal dysfunction leading to diabetic nephropathy.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.1
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• pp.43-48
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• 2013

Cisplatin is a anti-neoplastic agent which is commonly used for the treatment of solid tumor. Cisplatin activates multiple signal transduction pathways involved in the stress-induced apoptosis in a variety of cell types. Previous study reported that cisplatin induces apoptosis through activation of ERK, p38 and JNK in rat mesangial cells, but apoptotic pathway remain known. The present study investigated the apoptotic pathway for cisplatin-indcued apoptosis in rat mesangial cells. cisplatin-induced apoptosis was associated with activation of caspase-3, caspase-8, caspase-9. Caspase-8 inhibition prevented the activation of both caspase-3 and caspase-9. In addition, cisplatin-induced apoptosis increased the expression of Bax, but not the level of Bcl-2. These change of Bax/bcl-2 ratio caused the release of cytochrome c from mitochondria into cytosol. In previous study, the ethanol extract of Bojungbangam-tang (EBJT) inhibited cisplatin-induced apoptosis in rat mesangial cells through inhibition of ERK and JNK activation. However, EBJT did not increase cell proliferation, because it did not prevent cisplatin-induced G2/M phase arrest. These effect of EBJT may be related to p38 activation. Cisplatin-induced G2/M phase arrest are inhibited by treatment with p38 inhibitor and EBJT in rat mesangial cells. Also, p38 inhibition and EBJT treatment on cisplatin-induced G2/M phase arrest are markedly increased the G0/G1 phase and reduced the sub-G1. In conclusion, anti-apoptotic effet of EBJT did not increases cell proliferation, because EBJT did not reduce p38 activation related to cisplatin-induced G2/M phase arrest.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.6
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• pp.513-520
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• 2023

Cornuside is a secoiridoid glucoside compound extracted from the fruits of Cornus officinalis. Cornuside has immunomodulatory and anti-inflammatory properties; however, its potential therapeutic effects on diabetic nephropathy (DN) have not been completely explored. In this study, we established an in vitro model of DN through treating mesangial cells (MMCs) with glucose. MMCs were then treated with different concentrations of cornuside (0, 5, 10, and 30 μM). Cell viability was determined using cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays. Levels of proinflammatory cytokines, including interleukin (IL)-6, tumor necrosis factor-α, and IL-1β were examined using enzyme-linked immunosorbent assay. Reverse transcription quantitative real-time polymerase chain reaction and Western blotting were performed to detect the expression of AKT and nuclear factor-kappa B (NF-κB)-associated genes. We found that cornuside treatment significantly reduced glucose-induced increase in MMC viability and expression of pro-inflammatory cytokines. Moreover, cornuside inhibited glucose-induced phosphorylation of AKT and NF-κB inhibitor alpha, decreased the expression of proliferating cell nuclear antigen and cyclin D1, and increased the expression of p21. Our study indicates that the anti-inflammatory properties of cornuside in DN are due to AKT and NF-κB inactivation in MMCs.

• Childhood Kidney Diseases
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• v.1 no.2
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• pp.130-135
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• 1997

Purpose : Interleukin-6(IL-6), a multifunctional cytokine, has been found to have growth and differentiation activities on a wide variety of tissues and cells, including mesangial cells. It has been known that IL-6 is an autocrine growth factor for the proliferation of mesangial cells. Several studies have been performed for revealing the clinical significance of IL-6 in mesangial proliferative glomerulonephritis. Methods : The author measured serum and urinary IL-6 in 30 patients with $Henoch-Sch\"{o}nlein$ purpura (HSP), 18 patients with HSP nephritis, and 10 normal children as a control group. Results : The serum level of IL-6 was increased significantly in the patients with HSP and HSP nephritis compared to normal control. The level of urinary IL-6 was increased significantly in the patients with HSP nephritis compared to both HSP and normal control groups. The level of urinary IL-6 was not correlated with the level of serum. Conclusion : IL-6 was correlated with the amount of proteinuria. These data suggest that IL-6 may be involved in the pathological proliferation of mesangial cell in HSP nephritis.

• Childhood Kidney Diseases
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• v.10 no.1
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• pp.83-88
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• 2006

Orthostatic or postural proteinuria is a benign condition characterized by the presence of protein in urine samples collected in the upright position during the day and its absence in the supine position. Recently, nutcracker phenomenon has been documented as the source of postural proteinuria. The nutcracker phenomenon refers to compression of the left renal vein between the aorta and superior mesenteric artery, resulting in elevation of pressure in the left renal vein, leading to congestion of the left kidney and occasionally to collateral veins formation. Entrapment of the left renal vein is a cause of left-sided gross hematuria, ureteral and peripelvic varices, unexplained left flank pain and variable degrees of orthostatic proteinuria. We report the case of a 14-year-old girl with orthostatic proteinuria, diagnosed as having nutcracker syndrome by doppler sonography and MR angiography. Because daily protein excretion was more than 1.5 grams over 3 years of follow up, we decided to perform a renal biopsy which revealed moderate mesangial cell proliferation in all glomeruli.

• Korean Journal of Plant Resources
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• v.26 no.5
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• pp.652-657
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• 2013

In the present study, anti-oxidative and the RMC proliferation inhibitory propeties of 80% ethanol extracts from 63 kinds of traditional medicines were investigated. Inhibitory effects of RMC proliferation were showed that Dalbergia odorifera T. Chen., Melia azedarach Linn$\acute{e}$ and Hydnocarpus anthelmintica Pierre. Among them Hydnocarpus anthelmintica Pierre had the highest anti-oxidative activity ($ORAC_{PE\;value}=1.6$, DPPH = 81.1), but Dalbergia odorifera T. Chen. and Melia azedarach Linn$\acute{e}$ had no effects. These results suggest that the Hydnocarpus anthelmintica Pierre could prevent or protect from kidney disease as antioxidant and anti-proliferative agent for RMC.

• Proceedings of the Korean Society of Life Science Conference
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• 2007.10a
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• pp.96.1-96.1
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• 2007

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