Molecular analysis of type IV collagen accumulation in diabetic nephropathy
Molecular analysis of type IV collagen accumulation in diabetic nephropathy
批准号:
05670853
负责人:
KIKKAWA Ryuichi
金额:
$1.34万
依托单位国家:
日本
项目类别:
Grant-in-Aid for General Scientific Research (C)
财政年份:
1993
资助国家:
日本
项目状态:
已结题
起止时间:
1993 至 1994
中文摘要
肾小球系膜扩张被认为是糖尿病肾病的主要病变。损伤是由各种基质蛋白的积累引起的,尤其是IV型胶原。因此,了解IV型胶原是如何在系膜区积聚的,对于阐明糖尿病肾病的发病机制具有重要意义。我们已发表的文献表明,高浓度葡萄糖通过其代谢作用促进肾小球系膜细胞IV型胶原的产生。为了探讨葡萄糖促进IV型胶原产生的机制,我们在体外培养的大鼠肾小球系膜细胞中分析了IV型胶原的产生与高浓度葡萄糖代谢结果之间的联系。高浓度葡萄糖可显著激活蛋白激酶C(PKC)和丝裂原相关蛋白(MAP)。各种能够激活PKC和MAPK的血管活性物质可以刺激IV型胶原的产生。然而,高糖条件下培养的肾小球系膜细胞VI(Alpha_1)的Northern印迹杂交未检测到IV型胶原基因表达水平的任何变化。参与IV型胶原降解的基质金属蛋白酶-2和-9的mRNAs在上述实验中均未发生改变,提示葡萄糖可激活PKC和MAPK,进而刺激IV型胶原的产生,这可能与IV型胶原在糖尿病肾小球中的积聚有关。
英文摘要
The mesangial expansion in glomerulis considered to be a cardinal lesion of diabetic nephropathy. The lesion is caused by the accumulation of various matrix proteins, especially of type IV collagen. So, it is important to know how type IV collagen accumulate in mesangial area in order to clarify the pathogenesis of diabetic nephropathy.We have previous published that high concentration of glucose increases type IV collagen production in glomerular mesangial cells via its metabolic effect. In an attempt to investigate the mehanism why glucose increases type IV collagen production, the linkage between type IV collagen production and metabolic consequences to high concentration of glucose was analyzed in rat cultured mesangial cells. High concentration of glucose caused significant activation of protein kinase C (PKC) as well as of mitogen-associated protein (MAP) kinase. Various vasoactive substances, which are able to activate PKC and MAP kinase, are observed to stimulate type IV collagen production. However, any change in mRNA level for type IV collagen was not detected by northern blotting using VI (alpha_1) cDNA in mesangial cells cultured under high glucose condition. mRNAs for MMP-2 and -9, which were responsible for degrading type IV cllagen were neither changed in those experiments.It is concluded from these results that glucose may activate PKC and MAP kinase, and may in turn stimulate type IV collagen production, which might be associated with the accumulation of type IV collagen in diabetic glomeruli.
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Sugimoto T,Kikkawa R,et al: "Atrial natriuretic peptide inhibits endothelin-I-induced activation of mitogen-activated protein kinase in" Biochem Biophys Res Commun. 195. 72-78 (1993)
Sugimoto T、Kikkawa R 等人:“心房钠尿肽抑制内皮素-I 诱导的丝裂原激活蛋白激酶的激活”,Biochem Biophys Res Commun。
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Sawada T: "Amelioration by aldose reductase inhibitors of type IV collagen production in cultured rat mesangial cells under high glucose condition" US-Japan aldose reductase workshop. 4 (1994)
Sawada T:“在高葡萄糖条件下通过醛糖还原酶抑制剂改善培养的大鼠系膜细胞中 IV 型胶原蛋白的产生”美日醛糖还原酶研讨会。
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Sugimoto T, Kikkawa R,: "Atrial natriuretic peptide inhibits endothelin- I - induced activation of mitogen-activated protein kinase in cultured rat mesangial cells." Biochem Bjophys Res Commun. 195. 72-78 (1993)
Sugimoto T,Kikkawa R,:“心房钠尿肽抑制培养的大鼠系膜细胞中内皮素-I 诱导的丝裂原激活蛋白激酶的激活。”
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Kikkawa R,Haneda M,et al: "Atrial natriuretic peptide inhibits endothelin-I-induced activation of mitogen-activated protein kinase in cultured rat mesangial cells." Diabetologia. 37. 838-841 (1994)
Kikkawa R、Haneda M 等人:“心房钠尿肽抑制培养的大鼠系膜细胞中内皮素-I 诱导的丝裂原激活蛋白激酶的激活。”
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羽田勝計: "糖尿病学の進歩 第27巻" 日本糖尿病学会編,診断と治療社, 243 (1993)
Katsuke Haneda:《糖尿病学进展第 27 卷》日本糖尿病学会编辑,Diagnosis and Herosha,243(1993)
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共 12 条
Development of the treatment of diabetic nephropathy by targeting the TGF-β signaling
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财政年份:2000
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依托单位:
The molecular mechanism of increase of TGF-β expression in diabetic glomeruli
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Molecular analysis of glucose transporter in glomerular mesangial cells
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A Role of Gene Expression of Aldose Reductase in the Development of Diabetic Complications
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负责人:KIKKAWA Ryuichi
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依托单位:
海外基金