The effects of heparin on the expression of transforming growth factor-β 1 (TGF-β 1) and two extracellular matrix components laminin (LN) and fibronectin (FN) in diabetic rat glomeruli were investigated. Twent...The effects of heparin on the expression of transforming growth factor-β 1 (TGF-β 1) and two extracellular matrix components laminin (LN) and fibronectin (FN) in diabetic rat glomeruli were investigated. Twenty-six rats were randomly divided into control group (C, n=8), diabetic group (D, n=9), and diabetes+heparin group (DH, n=9). After 8-week therapy of heparin (200 U once daily by abdominal injection), TGF-β 1, LN and FN expression in glomeruli was detected by immunohistochemical method. The results showed that the expression levels of TGF-β 1, LN and FN were higher in group D than in group C. It was found that heparin could reduce 24-h urinary albumin excretion and inhibit overexpression of TGF-β 1, LN and FN in glomeruli of diabetic rats. It suggested that the inhibitory effect of heparin on diabetic glomerular sclerosis was at least partly related with the inhibition of TGF-β 1 expression.展开更多
目的观察高糖和AG490对大鼠肾小球系膜细胞Janus激酶/信号转导和转录活化因子(Januskinase/signal transducer and activators of transcription,JAK/STAT)信号激活以及对系膜细胞转化生长因子β1(transforming growth factor-β1,TGF-...目的观察高糖和AG490对大鼠肾小球系膜细胞Janus激酶/信号转导和转录活化因子(Januskinase/signal transducer and activators of transcription,JAK/STAT)信号激活以及对系膜细胞转化生长因子β1(transforming growth factor-β1,TGF-β1)和细胞外基质蛋白表达的影响。方法体外培养大鼠肾小球系膜细胞,分别给予高糖和AG490干预,采用免疫沉淀和Western印迹检测JAK2磷酸化表达,Western印迹检测信号蛋白STAT1、STAT3、磷酸化-STAT1(phospho-STAT1,p-STAT1)和p-STAT3表达;酶联免疫吸附实验(enzyme-linkedimmunoadsorbent assay,ELISA)和放射免疫法测定细胞上清液中TGF-β1、纤维连接蛋白(fibronectin,FN)和IV型胶原的分泌,逆转录-聚合酶链反应(reverse transcription and polymerase chain reaction,RT-PCR)检测TGF-β1mRNA表达。结果与低糖对照组比较,高糖培养的系膜细胞JAK2、p-STAT1和p-STAT3表达明显上调,TGF-β1、FN和IV型胶原分泌增加,TGF-β1mRNA表达增加;AG490能够明显抑制高糖培养系膜细胞JAK2的磷酸化,下调p-STAT1和p-STAT3表达,明显抑制TGF-β1、FN和Ⅳ型胶原的分泌,同时降低TGF-β1mRNA表达。结论JAK/STAT信号途径参与高糖诱导的肾小球系膜细胞TGF-β1和细胞外基质的分泌。展开更多
Objective Diabetic nephropathy （DN） is the major cause of end-stage renal disease worldwide and its prevalence continues to increase.Currently,therapies for DN provide only partial renoprotection; hence new targets ...Objective Diabetic nephropathy （DN） is the major cause of end-stage renal disease worldwide and its prevalence continues to increase.Currently,therapies for DN provide only partial renoprotection; hence new targets for therapeutic intervention need to be identified.In this review,we summarized the new target,sphingosine kinase-1/sphingosine 1-phosphate （SphK1/S1P） pathway,explored its potential therapeutic role in the prevention and treatment of DN.Data sources Most relevant articles were mainly identified by searching PubMed in English.Study selection Mainly original articles and critical review articles by major pioneer investigators in this field were selected to be reviewed.Results SphK1/S1P pathway can be activated by hyperglycemia,advanced glycation end products,and many proinflammatory cytokines,which leads to fibronectin,transforming growth factor-31 up-regulation and AP-1 activation.And then it could promote glomerular mesangial cells proliferation and extracellular matrix accumulation,mediating the initiation and progression of diabetic renal fibrosis.Conclusions SphK1/S1P pathway is closely correlated with the pathogenesis of DN.The results suggest that SphK1/ S1P pathway as a new target for clinically improving DN in future is of great prospect.展开更多
文摘The effects of heparin on the expression of transforming growth factor-β 1 (TGF-β 1) and two extracellular matrix components laminin (LN) and fibronectin (FN) in diabetic rat glomeruli were investigated. Twenty-six rats were randomly divided into control group (C, n=8), diabetic group (D, n=9), and diabetes+heparin group (DH, n=9). After 8-week therapy of heparin (200 U once daily by abdominal injection), TGF-β 1, LN and FN expression in glomeruli was detected by immunohistochemical method. The results showed that the expression levels of TGF-β 1, LN and FN were higher in group D than in group C. It was found that heparin could reduce 24-h urinary albumin excretion and inhibit overexpression of TGF-β 1, LN and FN in glomeruli of diabetic rats. It suggested that the inhibitory effect of heparin on diabetic glomerular sclerosis was at least partly related with the inhibition of TGF-β 1 expression.
文摘目的观察高糖和AG490对大鼠肾小球系膜细胞Janus激酶/信号转导和转录活化因子(Januskinase/signal transducer and activators of transcription,JAK/STAT)信号激活以及对系膜细胞转化生长因子β1(transforming growth factor-β1,TGF-β1)和细胞外基质蛋白表达的影响。方法体外培养大鼠肾小球系膜细胞,分别给予高糖和AG490干预,采用免疫沉淀和Western印迹检测JAK2磷酸化表达,Western印迹检测信号蛋白STAT1、STAT3、磷酸化-STAT1(phospho-STAT1,p-STAT1)和p-STAT3表达;酶联免疫吸附实验(enzyme-linkedimmunoadsorbent assay,ELISA)和放射免疫法测定细胞上清液中TGF-β1、纤维连接蛋白(fibronectin,FN)和IV型胶原的分泌,逆转录-聚合酶链反应(reverse transcription and polymerase chain reaction,RT-PCR)检测TGF-β1mRNA表达。结果与低糖对照组比较,高糖培养的系膜细胞JAK2、p-STAT1和p-STAT3表达明显上调,TGF-β1、FN和IV型胶原分泌增加,TGF-β1mRNA表达增加;AG490能够明显抑制高糖培养系膜细胞JAK2的磷酸化,下调p-STAT1和p-STAT3表达,明显抑制TGF-β1、FN和Ⅳ型胶原的分泌,同时降低TGF-β1mRNA表达。结论JAK/STAT信号途径参与高糖诱导的肾小球系膜细胞TGF-β1和细胞外基质的分泌。
基金This work was supported by research grants from the Natural Science Foundation of China （No. 81170676, 81373457） and Natural Science Foundation of Guangdong Province （No.S2012020010991, S2013010015765）.
文摘Objective Diabetic nephropathy （DN） is the major cause of end-stage renal disease worldwide and its prevalence continues to increase.Currently,therapies for DN provide only partial renoprotection; hence new targets for therapeutic intervention need to be identified.In this review,we summarized the new target,sphingosine kinase-1/sphingosine 1-phosphate （SphK1/S1P） pathway,explored its potential therapeutic role in the prevention and treatment of DN.Data sources Most relevant articles were mainly identified by searching PubMed in English.Study selection Mainly original articles and critical review articles by major pioneer investigators in this field were selected to be reviewed.Results SphK1/S1P pathway can be activated by hyperglycemia,advanced glycation end products,and many proinflammatory cytokines,which leads to fibronectin,transforming growth factor-31 up-regulation and AP-1 activation.And then it could promote glomerular mesangial cells proliferation and extracellular matrix accumulation,mediating the initiation and progression of diabetic renal fibrosis.Conclusions SphK1/S1P pathway is closely correlated with the pathogenesis of DN.The results suggest that SphK1/ S1P pathway as a new target for clinically improving DN in future is of great prospect.
