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EFFECTS OF RAPAMYCIN ON INTRAcellULAR CHOLESTEROL HOMEOSTASIS OF glomerular mesangial cell IN THE PRESENCE OF INTERLEUKIN-1β

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Chinese Medical Sciences Journal 2008年第4期23卷 205-211页

作者： Guo-iuan Zhang Hang Li Xue-wang Li Department of Nephrology Peking Union Medical College Hospital Chinese Academy of Medical Sciences ＆ Peking Union Medical College Beijing 100730

Objective To investigate the effects of rapamycin on cholesterol homeostasis of glomerular mesangial cells and the underlying mechanisms. Methods Intracellular cholesterol accumulation was measured by Oil Red O staining and high performance liquid chromatography. The effects of rapamycin on interleukin-1β（1L-1β）-induced mRNA and protein changes of low-density lipoprotein receptor （LDLR） and ATP-binding cassette transporter Al （ABCAl） were assayed by quantitative real-time PCR and Western blot. Transient expressions of 3 types of mammalian target of rapamycin （mTOR）, including mTOR-WT （wild type）, mTOR-RR （rapamycin resistant, with kinase activity）, and mTOR-RR-KD （rapamycin resistant, without kinase activity）, were obtained by plasmid transfection. Results Rapamycin had no significant influence on intracellular cholesterol concentration trader normal condition, but it significantly decreased the intracellular cholesterol concentration in the presence of IL-1β. Rapamycin dose-dependently suppressed the increased expression of LDLR induced by IL-1β and up-regulated the suppressed expression of ABCAl caused by IL-1β Transient expression of 3 types of mTOR all reduced ABCAl mRNA expression significantly, which all could be overroded by rapamycin. Conclusions Rapamycin may contribute to the maintaining of glomerular mesangial cell intracellular cholesterol homeostasis under inflammatory state by both reducing cholesterol uptake and increasing cholesterol effiux. And the effect may be not completely mediiated by mTOR.

关键词： rapamycin glomerular mesangial cell cholesterol low-density lipoprotein receptor ATP-binding ca, sette transporter A1

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Effects of emodin on the proliferation of the glomerular mesangial cell and correlative cytokines in rats

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Journal of Nanjing Medical University 2007年第5期21卷 298-301页

作者： Xili Wu Wanggang Zhang Wansen Sun Chenglin Qiao Department of Integrated Chinese Traditional and Western Medicine the Second Affiliated Hospital of Xi＇ an Jiaotong University Xi＇ an 710004 Shanxi Province China Department of Hematology the Second Affiliated Hospital of Xi＇ an Jiaotong University Xi＇ an 710004 Shanxi Province China

Objective：To investigate the effects of emodin（EMD） on cell proliferation and correlative cytokines secretion of glomerular mesangial in rats. Methods：The effects of EMD on cell proliferation and IL-6, TGF-β1 secretion of glomerular mesangial in rats were observed. cell proliferation was measured by MTT method. IL-6 and TGF-β1 secretion was detected with ELISA. Results：EMD was able to inhibit the cell proliferation and down-regulate the IL-6 and TGF-β 1 secretion of glomerular mesangial, as compared to the model group in rats （P 〈 0.05）. Conclusion：EMD could significantly inhibit the cell proliferation, and reduce the creation of extracellular matrix（ECM）, this indicated that it could play an important role in alleviation and prevention of glomerular sclerosis. The mechanism may be that EMD can reduce the IL-6 and TGF-β1 secretion ofglomerular mesangial cell in rats.

关键词： emodin glomerular mesangial cell mesangial cell proliferation correlative cytokines

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Isolation and Purification of Polysaccharides from Cordyceps minlitaris and Its Inhibition on the Proliferation of Rat glomerular mesangial cells

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Chemical Research in Chinese Universities 2008年第5期24卷 584-587页

作者： HOU A-li MENG Qing-fan AN Jin-shuang ZHU Kai FENG Yun TENG Li-rong College of Life Science Jilin University Changchun 130012 P. R. China

The crude polysaccharide was obtained by means of the decolorization of porphyrized Cordyceps minlitaris stroma with organic solvent, extraction with hot water, precipitation in 80% ethanol, and protein removal with the Sevag method. After purification with Sephadex G-75, two of its components, CMP-1 and CMP-2, were obtained. Through the assay of gel chromatography and polarimetry, CMP-1 was identified as pure polysaccharide. The results demonstrated that CMP-1 had favorable oxidation resistance activity, which could scavenge not only oxygen-free radicals in the self-oxidation system of pyrogallic acid, but also the hydroxide-free radicals in the Fenton system. The study focused on the effects of low, medium, and high dosages of CMP-1 in rat blood serum on the proliferation of glomerular mesangial cells in vitro. Through MTT Colorimetric analysis, the activities were compared among the blank control group and the Niaoduqing positive control group CMP-1 and CMP-2. The results shows that CMP-1 was able to inhibit the proliferation of rat glomerular mesangial cells effectively. Therefore, CMP-1, one component of polysaccharides of Cordyceps minlitaris, was certainly a potential remedy for hyperplastic glomerular nephritis, whose antioxidant activity could slow down the process of chronic renal failure（CRF） to some extent.

关键词： Cordyceps minlitaris Polysaccharide glomerular mesangial cell Oxidation resistance Chronic renal failure

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Metformin inhibits nuclear factor-κB activation and inflammatory cytokines expression induced by high glucose via adenosine monophosphate-activated protein kinase activation in rat glomerular mesangial cells in vitro

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Chinese Medical Journal 2014年第9期127卷 1755-1760页

作者： Gu Junfei Ye Shandong Wang Shan Sun Wenjia Hu Yuanyuan Department of Endocrinology Anhui Provincial Hospital Affiliated to Anhui Medical University Hefei Anhui 230001 China

Background The renoprotective mechanisms of adenosine monophosphate （AMP）-activated protein kinase （AMPK） agonist-metformin have not been stated *** hypothesized that metformin may ameliorate inflammation via AMPK interaction with critical inflammatory cytokines The aim of this study was to observe the effects of metformin on expression of nuclear factor-κB （NF-κB）,monocyte chemoattractant protein-1 （MCP-1）,intercellular adhesion molecule-1 （ICAM-1） and transforming growth factor-beta 1 （TGF-β1） induced by high glucose （HG） in cultured rat glomerular mesangial cells （MCs）.Methods MCs were cultured in the medium with normal concentration glucose （group NG,5.6 mmol/L）,high concentration glucose （group HG,25 mmol/L） and different concentrations of metformin （group M1,M2,M3）.After 48-hour exposure,the supernatants and MCs were *** expression of NF-κB,MCP-1,ICAM-1,and TGF-β1 mRNA was analyzed by real time polymerase chain *** blotting was used to detect the expression of AMPK,phospho-Thr-172 AMPK （p-AMPK）,NF-κB p65,MCP-1,ICAM-1,and TGF-β1 *** After stimulated by HG,the expression of NF-κB,MCP-1,ICAM-1,TGF-β1 mRNA and protein of MCs in group HG increased significantly compared with group NG （P ＜0.05）.Both genes and protein expression of NF-κB,MCP-1,ICAM-1,TGF-β1 of MCs induced by high glucose were markedly reduced after metformin treatment in a dose-dependent manner （P ＜0.05）.The expression of p-AMPK increased with the rising of metformin concentration,presenting the opposite trend,while the level of total-AMPK protein was unchanged with exposure to HG or *** Metformin can suppress the expression of NF-κB,MCP-1,ICAM-1 and TGF-β1 of glomerular MCs induced by high glucose via AMPK activation,which may partlv contribute to its reno-protection.

关键词： metformin adenosine monophosphate-activated protein kinase nuclear factor-κB, monocyte chemoattractant protein-1 intercellular adhesion molecule-1 transforming growth factor-beta 1 glomerular mesangial cell

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The gene expression profile and overexpression of apoptosis-related genes (NGFI-B and Gadd 45γ) in early phase of Thy-1 nephritis model

The gene expression profile and overexpression of apoptosis-...

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中国免疫学会第五届全国代表大会暨学术会议

作者： Jing-hua Xu, Wen Qiu, Ying-wei Wang, Juan Xu, Jian-xia Tong, Ling-juan Gao, Wen-huang Xu, Yi-qin Wu (Department of Immunology, Nanjing Medical University, Nanjing, 210029, China Corresponding author, Department of Immunology, Nanjing Medical University, Nanjing Hanzhong Road 140 , Jiangsu Province, 210029, China.

Mesangioproliferative glomerulonephritis ( MPGN) is a disease of high incidence in humans. Rat Thy-1 nephritis (Thy-1 N) , namely, anti-thymocyte serum ( ATS)-induced nephritis is usually considerated to be an animal model for studying MPGN. Although previous studies demonstrated that the glomerular mesangial cells (GMCs) injury was thought to be a feature of Thy-1 N, the mechanism of the disease (i. e. GMCs apoptosis) remains unclear.

关键词： Thy-1 nephritis glomerular mesangial cell Apoptosis NGFI-B Gadd45γ

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