Effect of endothelin-1 (1-31) on human mesangial cell proliferation.
Effect of endothelin-1 (1-31) on human mesangial cell proliferation.
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内皮素-1 (1-31) 对人系膜细胞增殖的影响。
DOI：
10.1254/jjp.84.146
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
T. Tamaki
中科院分区：
文献类型：
--
作者：
M. Yoshizumi;S. Kagami;Y. Suzaki;K. Tsuchiya;H. Houchi;T. Hisayama;H. Fukui;T. Tamaki
先前发现，人凝乳酶在Tyr31-Gly32键上裂解大内皮素(ETS)，产生31个氨基酸的ETS(1-31)。本研究检测了人血浆中ET-1(1-31)和ET-1的浓度，并观察了人工合成的ET-1(1-31)对体外培养的人肾小球系膜细胞(HMCs)增殖的影响。以[~3H]-胸腺嘧啶核苷摄取率为指标评价ET-1(1-31)的促增殖作用。细胞外信号调节蛋白(ERK)活性和激活蛋白-1的DNA结合活性分别采用凝胶内激酶法和凝胶迁移率改变法检测。血浆中可检测到免疫活性ET-1(1-31)，但水平略低于ET-1。ET-1(1-31)可使HMCS[~3H]-胸腺嘧啶核苷掺入增加，其作用与ET-1相似。ET-1(1-31)也可激活ERK1/2。抑制蛋白激酶C和ERK激酶可降低ET-1(1-31)诱导的ERK1/2的激活。在ERK1/2激活之后，转录因子激活蛋白-1DNA结合活性增加。这些发现表明，ET-1(1-31)是人体内的一种生物活性多肽，ET-1(1-31)本身具有刺激HMC增殖的作用。
It was previously found that human chymase cleaves big endothelins (ETs) at the Tyr31-Gly32 bond and produces 31-amino acid ETs (1-31). In the present study, human plasma concentrations of ET-1 (1-31) and ET-1 were examined and the effect of synthetic ET-1 (1-31) on the proliferation of cultured human mesangial cells (HMCs) was investigated. The proliferative effect of ET-1 (1-31) was evaluated from the [3H]-thymidine uptake. The activity of extracellular signal-regulated kinase (ERK) and DNA binding activity of activator protein-1 were determined by using an in-gel kinase assay and gel mobility shift assay, respectively. Immunoreactive ET-1 (1-31) was detectable in plasma, but the level was slightly lower than that of ET-1. ET-1 (1-31) increased [3H]-thymidine incorporation in HMCs to a degree similar to that induced by ET-1. ET-1 (1-31) also activated ERK1/2. Inhibition of protein kinase C and ERK kinase caused a reduction of ET-1 (1-31)-induced ERK1/2 activation. The ERK1/2 activation was followed by an increase in transcription factor activator protein-1 DNA binding activity. These findings suggest that ET-1 (1-31) is a bioactive peptide in humans and ET-1 (1-31) itself stimulates HMC proliferation.
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DOI：
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发表时间：
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期刊：
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影响因子：
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DOI：
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发表时间：
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期刊：
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DOI：
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发表时间：
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期刊：
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影响因子：
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