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| 1 | A novel compound AB38b attenuates oxidative stress and ECM protein accumulation in kidneys of diabetic mice through modulation of Keap1/Nrf2 signaling显示文摘Extracellular matrix(ECM)deposition following reactive oxygen species(ROS)overproduction has a key role in diabetic nephropathy(DN),thus,antioxidant therapy is considered as a promising strategy for treating DN.Here,we investigated the therapeutic effects of AB38b,a novel syntheticα,β-unsaturated ketone compound,on the oxidative stress(OS)and ECM accumulation in type 2 diabetes mice,and tried to clarify the mechanisms underlying the effects in high glucose(HG,30 mM)-treated mouse glomerular mesangial cells(GMCs).Type 2 diabetes model was established in mice with high-fat diet feeding combined with streptozocin intraperitoneal administration.The diabetic mice were then treated with AB38b(10,20,40 mg·kg^?1·d^?1,ig)or a positive control drug resveratrol(40 mg·kg^?1·d^?1,ig)for 8 weeks.We showed that administration of AB38b or resveratrol prevented the increases in malondialdehyde level,lactate dehydrogenase release,and laminin and type IV collagen deposition in the diabetic kidney.Simultaneously,AB38b or resveratrol markedly lowered the level of Keap1,accompanied by evident activation of Nrf2 signaling in the diabetic kidney.The underlying mechanisms of antioxidant effect of AB38b were explored in HG-treated mouse GMCs.AB38b(2.5?10μM)or resveratrol(10μM)significantly alleviated OS and ECM accumulation in HG-treated GMCs.Furthermore,AB38b or resveratrol treatment effectively activated Nrf2 signaling by inhibiting Keap1 expression without affecting the interaction between Keap1 and Nrf2.Besides,AB38b treatment effectively suppressed the ubiquitination of Nrf2.Taken together,this study demonstrates that AB38b ameliorates experimental DN through antioxidation and modulation of Keap1/Nrf2 signaling pathway. | Lei Du Lei Wang Bo Wang Jin Wang Meng Hao Yi-bing Chen Xi-zhi Li Yuan Li Yan-fei Jiang Cheng-cheng Li Hao Yang Xiao-ke Gu Xiao-xing Yin Qian Lu | 2020 | Acta Pharmacologica Sinica2020，41，3： | 13 |
| 2 | Role of IL-10 in the progression of kidney disease显示文摘Interleukin-10(IL-10), a cytokine with anti-inflammatory and immunomodulatory functions, regulates the biology of B and T cells. The present review describes the role of IL-10 in normal renal physiology, during acute kidney injury and in the development of chronic renal failure. We further discuss IL-10-induced cellular and molecular pathways and their link to the progression of kidney injury. | Inna Sinuani Ilia Beberashvili Zhan Averbukh Judith Sandbank | 2013 | World Journal of Transplantation2013，3，4： | 11 |
| 3 | 活血化瘀中药抗系膜细胞增殖的作用机制分析显示文摘系膜细胞(mesangial cell,MsC)是肾小球重要的固有细胞之一,在慢性肾脏病(CKD)的发病过程中,系膜细胞占据着重要位置。多种致病因素导致系膜细胞增殖及合成细胞外基质(ECM)增加,是慢性肾小球肾炎发生、发展及肾小球硬化的重要病理基础,减少以至使MsC、ECM趋于生理状态,可以阻止CKD的进展。故而设法抑制系膜细胞增殖、减少ECM的聚集,对于CKD的治疗具有重要意义。 | 赵姗姗 姚源璋 | 2016 | 中国中西医结合肾病杂志2016，17，2： | 7 |
| 4 | Jixuecao(Herba Centellae Asiaticae) alleviates mesangial cell proliferation in IgA nephropathy by inducing mitofusin 2 expression显示文摘OBJECTIVE:To investigate the effect of mitofusin 2 (Mfn2) and its downstream signaling pathway on glomerular mesangial cells (GMCs) proliferation in IgA nephropathy (IgAN),as well as the mechanism of action of Jixuecao (Herba Centellae Asiaticae,HCA) in the treatment of IgAN.METHODS:Adenovirus-mediated Mfn2 gene transfection and Mfn2 expression were analyzed by real-time polymerase chain reaction (PCR) and Western blotting.IgA1 induced the proliferation of GMCs,which were then treated with HCA.Cell proliferation was detected with cell counting kit-8 (CCK-8),and Mfn2 expression was analyzed by real-time PCR and western blotting.An IgAN animal model was also established and treated with HCA.GMCs proliferation was detected by hematoxylin-eosin staining,mitochondrial structure was analyzed by electron microscopy,mitochondrial function was determined by the Clark oxygen electrode method,and the expression of Mfn2,Phospho-extracellular regulated protein kinases1/2 (P-ERK1/2),Cyclin-dependent kinase 2 (CDK2),Phospho-p27 (p-p27),and cyclin A was analyzed by Western blotting.RESULTS:In vitro,HCA inhibited GMCs in a concentration-dependent manner in association with the upregulation of Mfn2 expression.The overexpression of Mfn2 inhibited IgA1-induced GMCs proliferation and elevated the effect of HCA.In vivo,treatment with HCA could alleviate albuminuria and creatinine and GMCs proliferation.These effects were related to the upregulation of Mfn2,p-p27 and inhibition of p-ERK1/2,CDK2,and cyclinA.Mitochondrial swelling,vacuolar degeneration,and reduction of respiratory control rate were identified in IgAN,but HCA could improve the mitochondrial structure and function.CONCLUSION:HCA inhibited GMCs proliferation via the upregulation Mfn2 and the inhibition of Ras-Raf-ERK/MAPK.We revealed that changes of mitochondrial structure and function are associated with IgAN,but that HCA can improve these mitochondrial features. | Chen Hongyu Du Yuanyuan Li Yayu Zeng Jiali Miao Jianxia Jiang Xue | 2019 | Journal of Traditional Chinese Medicine2019，39，3： | 6 |
| 5 | Upregulation of MiR-126 Delays the Senescence of Human Glomerular Mesangial Cells Induced by High Glucose via Telomere-p53-p21-Rb Signaling Pathway显示文摘Diabetic kidney disease (DKD)is a microvascular complication of type 2 diabetes.The study of DKD mechanisms is the most important target for the prevention of DKD.Renal senescence is one of the important pathogeneses for DKD,but the mechanism of renal and cellular senescence is unclear.Decreased expression of circulating miR-126 is associated with the development of DKD and may be a promising blood-based biomarker for DKD.This study is to probe the effect and mechanism of miR-126 on the aging of human glomerular mesangial cells (HGMCs)induced by high glucose.HGMCs were cultured with Roswell Park Memorial Institute (RPMI-1640)in vitro.The effect of high glucose on morphology of HGMCs was observed 72h after intervention.The cell cycle was examined by flow cytometry.The telomere length was measured by Southern blotting.The expression levels of p53,p21 and Rb proteins in p53-p21-Rb signaling pathway and p-statl,p-stat3 in JAK/STAT signaling pathway were detected by Western blotting respectively.The expression of miR-126 was examined by qRT-PCR.MiR-126 mimics was transfected into HGMCs.The effects of miR-126 mimics transfection on cell morphology,cell cycle,telomere length,p53,p21,Rb,p-stat1 and p-stat3 were observed. The results showed that high glucose not only arrested the cell cycle in G1phase but also shortened the telomere length.High glucose led to high expression of p53,p21,Rb,p-statl and p-stat3 and premature senescence of HGMCs by activating the telomere-p53-p21-Rb and JAK/STAT signaling pathways.Moreover,the miR-126 was decreased in HGMCs induced by high glucose.It was suggested that the transfection of miR-126 mimics could inhibit the telomere-p53-p21-Rb and JAK/STAT signaling pathway activity in vitro and delay the senescence of HGMCs.The results may serve as a new strategy for the treatment of DKD. | Dong-wei CAO Chun-ming JIANG Cheng WAN Miao ZHANC Qing-yan ZHANG Min ZHAO Bo YANG Da-long ZHU Xiao HAN | 2018 | Current Medical Science2018，38，5： | 5 |
| 6 | Effect of heparin on high glucose induced proliferation and expression of matrix metalloproteinases in normal human mesangial cells显示文摘Background The pathogenesis of diabetic nephropathy (DN) is a complex pathophysiological process.Its precise mechanism is not fully known. In recent years it has been recognized that synthesis of various extracelluar matrix (ECM) components may increase, and that degradation of ECM may decrease in DN. It was reported heparin could inhibit mesangial cells proliferation in vitro. The main aim of this study is to explore whether heparin inhibits proliferation of mesangial cells grown in high glucose concentration and to measure the effect of heparin on matrix metalloproteinases (MMPs) expression in mesangial cells. Methods The medium contained either low glucose (5 mmol/L) or high glucose (25 mmol/L). The concentrations of heparin in the culture medium were 0, 25, 50,100, 200 or 400 μg/mL. A metabolic (WST-1) assay was used to measure mesangial cell proliferation and Western blot analysis was used to measure MMPs expression of mesangial cells. Results Normal human mesangial cell (NHMC) proliferation was higher in high glucose (HG) medium than in low glucose (LG) medium. They showed a 1.93 fold expansion after 72 h in high glucose in contrast to a 1.63 fold expansion in low glucose. In the presence of heparin, mesangial cells proliferation was inhibited, which was more obvious at high glucose concentrations than at low glucose concentrations. In high glucose, with heparin concentration of 50, 100, 200 and 400 μg/mL, the mesangial cells showed a 0. 61 fold, 0.52 fold, 0.52 fold and 0.41 fold reductions in cell number compared to cells grown without heparin. In low glucose, only concentrations of 200 μg/mL and 400 μg/mL showed reduction in cell number, namely 0.54 fold and 0.45 fold, when compared to cells grown without heparin. In Western blot analysis,MMP1, MMP2, MMP3 and MMP9 was expressed by mesangial cells expressed in both high and low glucose concentrations, which was more prominent in high glucose medium. Incubation of heparin further increased expression of MMP1, MMP2, MMP3 and MMP9. Conclusions This study suggests that glucose can accelerate mesangial cell proliferation while heparin can reduce proliferation, being more obvious at high glucose concentrations. Higher glucose concentrations led to increased MMP expression, which may take part in the regulation of mesangial matrix synthesis and degradation. Addition of heparin resulted in a corresponding increase in MMP expression, most notably at high glucose concentrations, indicating a potentially renoprotective role in DN. | ZHOU Qiao-ling Yasumoto Yuichiro Tsukamoto Masatoshi Nozaki Tsuyoshi Sogabe Atsushi Harada Kouji ZHANG Yi-xiang LIN Xiao-yan ZHANG Yang-de Arima Terukatsu | 2005 | Journal of Central South University of Technology2005，12，z1： | 3 |
| 7 | 中医治疗系膜增生性肾小球肾炎近况显示文摘系膜增生性肾小球肾炎(mesangial proliferative glomerulonephritis,MsPGN)病理上表现以光镜下肾小球呈弥漫性系膜细胞增生和(或)系膜基质增多为特征的肾小球疾病[1],约占成人原发性肾小球疾病肾穿刺病例24.7%~30.3%[2]。根据免疫病理分为IgA肾病及非IgA系膜增生性肾小球肾炎两种类型。 | 周少婷 甘兰岚 谭海丽 黄国东 | 2018 | 实用中医药杂志2018，34，1： | 3 |
| 8 | AP-1 mediated signal transduction in thrombin induced regulation of PAL-1 expression in human mesangial cells显示文摘Objective To evaluate activator protein 1(AP 1) mediated mechanisms in thrombin induced qlasmino^gen activator inhibitor 1 (PAI 1) expression in cultured human glomerular mesangial cells (MCs) Methods Electrophoretic mobility shift assay (EMSA) was employed to assess AP 1 DNA binding activity, and Western blot hybridization was used for quantification of c fos and c jun, two subunits of AP 1 dimers PAI 1 activity and mRNA expression were analysed by the fibrin plate assay and Northern hybridization, respectively Results Thrombin concentration enhanced PAI 1 activity in the supernatant and stimulated PAI 1 mRNA expression in cultured MCs PAI 1 activity was blocked by hirudin, a specific inhibitor of thrombin Further study demonstrated that thrombin promoted AP 1 DNA binding activity but exerted little effect on c fos or c jun Curcumin (AP 1 inhibitor), staurosporine (PKC inhibitor), and genistein (PTK inhibitor) all reduced AP 1 mediated PAI 1 mRNA expression induced by thrombin in cultured MCs Conclusion The present study indicates that in cultured human MCs, thrombin stimulates PAI 1 expression through an AP 1 signal pathway, which may be mediated by PKC and | 陈香美 何庆南 刘文虎 徐启河 叶一舟 傅博 于力方 | 2000 | Chinese Medical Journal2000，，6： | 2 |
| 9 | Effectiveness of Qingre Lishi Yishen decoction on the glomerular fibrosis of immunoglobulin A nephropathy in a rat’s model显示文摘OBJECTIVE: To investigate the effect of the clinical effective prescription of Qingre Lishi Yishen decoction(QRLS) on the activation of mesangial cells in immunoglobulin A nephropathy(IgAN) rats.METHODS: IgAN rat’s model was established by combine with intragastric administration of bovine serum albumin(BSA) + intravenous injection of lipopolysaccharide(LPS) by + subcutaneous injection of carbon tetrachloride(CCL4). Then the animals were randomly divided into four groups: control group, IgAN model group, IgAN model with Valsartan(Val) treatment group and IgAN model with QRLS treatment group. To observe the indexes of 24-h urine protein, renal function, deposition of immune complexes, expression of activation factor, fibrosis marker and inflammatory cytokines in four different groups.RESULTS: The Val or QRLS treatment group:(a) it reduced the immune complexes deposition of IgA in glomerular mesangial and inhibited mesangial cell proliferation;(b) it decreased the expression of smooth muscle actin(α-SMA), fibronectin(FN) and tumor necrosis factor alpha(TNF-α).CONCLUSION: The study suggested that QRLS ameliorate renal structure and function in IgAN rat’s model. Furthermore, we also observed that QRLS alleviated mesangial cells activation and matrix accumulation partly by decreasing the α-SMA,then to downregulated the expression of FN and TNF-α. | Dang Wanyu Hou Linyi Yan Huimin Wu Xiaoming Zhen Xiaofang Hao Jing | 2019 | Journal of Traditional Chinese Medicine2019，39，4： | 2 |
| 10 | Effects of Cyclosporin A on Proliferation of Cultured Rat Mesangial Cells显示文摘The proliferation of mesangial cells on cyclosporin (CsA) test mediumwas studied by MTT assay and TNF-Q in cultured supernatant was examined byusing ELISA. The results showed that cyclosporin A significantly inhibited theproliferation of mesangial cells at the concentration between 0. 25 - 15 μg/ml(IC50 1μg/ml). This action appeared to be dose-dependent. Release of TNF-αfrom mesangial cells stimulated by LPS was also dose-dependently suppressed. Itis suggested that cyclosporin A play an important role in antiproliferation mecha-nism of mesangial cells in vitro. | 孙建平 王韵琴 | 1997 | Journal of Huazhong University of Science and Technology(Medical Sciences)1997，17，2： | 2 |
| 11 | Design and evaluation of glomerulus mesangium-targeted PEG-PLGA nanoparticles loaded with dexamethasone acetate显示文摘Mesangial proliferative glomerulonephritis (MsPGN),one of the most common glomerulonephritis pathological types,often leads to end-stage renal disease over a prolonged period.But the current treatment of MsPGN is non-specific and causes serious side effects,thus novel therapeutics and targeting strategies are urgently demanded.By combining the advantages of PEG-PLGA nanoparticles and the size selection mechanism of renal glomerulus,we designed and developed a novel PEG-PLGA nanoparticle delivery system capable of delivering dexamethasone acetate (A-DEX)into glomerular mesangium.We determined that 90 nm was the optimum size to encapsulate A-DEX for glomerular mesangium targeting based on the size-selection mechanism of glomerulus. After intravenous administration in rats,90 nm DiD-loaded NPs were found to accumulate to a greater extent in the kidney and kidneycortex compared with the free DiD solution.The 90 nm A-DEX NPs are also more stable at room temperature and showed a sustained release pattern.In rat glomerular mesangial cells (HBZY-1)in vitro,we found that the uptake of 90 nm A-DEX NPs was both temperature-dependent and energe-dependent,and they were mostly engulfed via clathrin-dependent endocytosis pathways,in summary,we have successfully developed a glomerular mesangium-targeted PEG-PLGA NPs,which is potential for the treatment of MsPGN. | Sha Li Ying-chun Zeng Ke Peng Chang Liu Zhi-rong Zhang Ling Zhang | 2019 | Acta Pharmacologica Sinica2019，40，1： | 2 |
| 12 | Clinico-pathological characteristics and prognosis of Ig A nephropathy patients with microalbuminuria and deposition of complement C3显示文摘Objective To analyze the clinical and pathological data and prognosis of Ig A nephropathy patients with microalbuminuria and deposition of C3,and to investigate the significance of C3 deposition in Ig A nephropathy with microalbuminuria.Methods The clinical and pathological data of 127 Ig A nephropathy patients with microalbu- | 郭宗运 | 2016 | China Medical Abstracts(Internal Medicine)2016，33，2： | 1 |
| 13 | 多发性大动脉炎合并膜增殖样肾小球病变一例报告显示文摘膜增殖性肾小球肾炎(membranoproliferative glomerulonephritis,MPGN),又名系膜毛细血管性肾小球肾炎(mesangial capillary glomerulonephritis,MCGN),其特点是肾小球基底膜增厚、系膜细胞增殖和系膜基质增多[1-2]。临床上患者常常表现为肾病综合征伴血尿、高血压和肾功能损害,部分患者伴有持续性低补体血症,故又称为低补体性慢性肾炎[3-5]。我院收治1例多发性大动脉炎合并膜增殖样肾小球病变患者,现报告如下。 | 郑维 耿晓东 吴镝 | 2015 | 中华肾病研究电子杂志2015，4，2： | 1 |
| 14 | Effect of Astragalin on matrix secretion and β1 integrin mRNA expression in human mesangial cells显示文摘Objective To investigate the effect of Astragalin on human renal mesangial cells Methods Cultured human mesangial cells were treated with Astragalin and Astragalin serum in different concentrations in the presence or absence of PDGF BB, the proliferation and type Ⅳ collagen secretion of mesangial cells were measured by MTT assay and ELISA, and expression of β1 integrin gene was estimated by reverse transcription polymerase chain reaction (RT PCR) method, sespectively Results After 72 hours Astragalin or Astragalin serum treatment, the proliferation of mesangial cells induced by PDGF BB was inhibited significantly in a dose dependent manner compared with untreated controls ( P <0 05 and P <0 01) After 24 hours of Astragalin or Astragalin serum treatment, the secretion of type Ⅳ collagen protein in presence of PDGF BB was significantly decreased and β1 integrin mRNA level decreased significantly compared with untreated control ( P <0 05, P <0 01) Conclusions Astragalin inhibits cell proliferation and matrix over synthesis which might be mediated, at least, partly by decrease of β1 integrin gene over expression The study suggested that Astragalin might play a role in preventing the progression of chronic renal | 倪兆慧 张庆怡 钱家麒 王利民 | 1999 | Chinese Medical Journal1999，，12： | 1 |
| 15 | Effect of rhein on glucose transporter-1 expression and its function in glomerular mesangial cells显示文摘Objective To explore the effect of rhein on the regulation of glucose transporter 1 (GLUT1) overexpression and the possible molecular mechanism that rhein antagonize the effect of transforming growth factor β1 (TGF β1) in glomerular mesangial cells Methods Cultured mouse mesangial cells were used The expression of GLUT1 mRNA was detected by Northern blotting; the ability of glucose uptake was determined by 2 deoxy [ 3H] D glucose uptake assay Results Rhein had no effect on glucose uptake in mesangial cells cultured in normal glucose concentration TGF β1 could upregulate the expression of GLUT1 mRNA and glucose uptake in mesangial cells This effect was markedly attenuated by the addition of rhein in a dose dependent manner Conclusions TGF β1 could upregulate the expression of GLUT1 mRNA and glucose uptake in mesangial cells, resulting in excessive glucose consumption and extracellular matrix production in diabetic nephropathy Rhein antagonized the effect of TGF β1 in mesangial cells, so it might be a hopeful remedy for the treatment of patients with diabetic | 章精 刘志红 陈朝红 李颖健 黎磊石 | 1999 | Chinese Medical Journal1999，，12： | 1 |
| 16 | Regulation of the expression and function of glucose transporter-1 by TGF- β1 and high glucose in mesangial cells显示文摘Objective To study the effects of high glucose and transforming growth factor β1 (TGF β1) on the expression and function of glucose transporter 1 (GLUT1) in mouse mesangial cells Methods Cultured mouse mesangial cells were used The expression of GLUT1 mRNA was detected by Northern Blot; glucose uptake and its kinetics were determined with a 2 Deoxy [ 3H] D glucose uptake assay Results Mesangial cells exposed to enriched glucose medium (20?mmol/L) for 72 hours demonstrated a decrease in both GLUT1 mRNA and V max for uptake of the glucose analog, 2 deoxy D glucose (2DOG), as compared to mesangial cells cultured in physiologic glucose concentrations(5 5?mmol/L) In contrast, hypertonic mannitol had no effect on GLUT1 mRNA levels TGF β1 treatment for 10 hours stimulated 2DOG uptake, both in 5 5?mmol/L and 20?mmol/L glucose medium, by approximately 4 28 fold in a dose dependent manner (2?ng/ml maximum) Kinetic analysis of 2DOG uptake revealed an increase in V max and a decrease in K m in the presence of TGF β1 TGF β1 also up regulated the expression of GLUT1 mRNA in mesangial cells The addition of anti TGF β neutralizing antibody (30?μg/ml) in mesangial cells cultured in enriched glucose medium (20?mmol/L) led to a 40% decrease in 2DOG uptake Conclusions The expression of GLUT1 can be suppressed by exposure of mesangial cells to high glucose medium, which may serve as a protective mechanism against possible adverse effects of excessive glucose flux into cells TGF β1 stimulates glucose uptake by enhancing the expression and function of GLUT1 in mesangial cells This effect is independent of the glucose milieu in the cultured | 章精 刘志红 刘浩 李颖健 黎磊石 | 2000 | Chinese Medical Journal2000，，6： | 0 |
| 17 | Effects and mechanism of Megsin gene transfection on mesangial cell proliferation and type Ⅳ collagen excretion显示文摘Objective To investigate the effects and mechanism of Megsin gene transfection on mesangial cell proliferation and typeⅣcollagen excretion. Methods Rat Megsin cDNA eukaryotic expressing vector was constructed and transfected to cultured rat mesangial cells. Cell proliferation was measured by determining [3H] -thymidine (3H-TdR) incorporation. The mRNA expression | 夏运风 | 2006 | China Medical Abstracts(Internal Medicine)2006，23，4： | 0 |
| 18 | Effect of simvastatin on PMA-induced expression of type A scavenger receptor in human glomerular mesangial cells显示文摘Objective To investigate the effects of simvastatin on inducible type A scavenger receptor (SR-A) in human glomerular mesangial cells (HMC). Methods HMC were cultured and stimulated with phorbol 12-myristate 13 -acetate (PMA). The uptake of fluorescence Dil-labeled acetylated LDL (Dil-Ac-LDL) by HMC was evaluated by confocal mi(?)roscopy.SR-A mRNA | 叶文玲 | 2006 | China Medical Abstracts(Internal Medicine)2006，23，4： | 0 |
| 19 | Protective effect and mechanism of MST1inhibition on kidney tissue in diabetic rats induced by streptozotocin显示文摘Objective To investigate the protective effect and mechanism of MST1 inhibition on kidney tissue in diabet-ic rats,and to find a new therapeutic target for diabetic nephropathy.Methods Total of 54 male SD rats enrolled in this study were divided into 3 groups including normal control(group A,n=18).MST1 inhibition | 吴蔚桦 | 2016 | China Medical Abstracts(Internal Medicine)2016，33，1： | 0 |
| 20 | Clinical and pathology features of idiopathic membranous nephropathy accompanied by mesangial dense deposit显示文摘Objective To investigate clinical and pathological features of idiopathic membranous nephropathy(IMN)accompanied by mesangial dense deposit.Methods Clinical data of 46 patients who were diagnosed as IMN accompanied by mesangial dense deposit admitted to Zhejiang Provincial People’s Hospital from January 2013 | 杨平 | 2016 | China Medical Abstracts(Internal Medicine)2016，33，1： | 0 |
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