PLATELET-DERIVED GROWTH-FACTOR (PDGF) AND PDGF RECEPTOR ARE INDUCED IN MESANGIAL PROLIFERATIVE NEPHRITIS IN THE RAT

PLATELET-DERIVED GROWTH-FACTOR (PDGF) AND PDGF RECEPTOR ARE INDUCED IN MESANGIAL PROLIFERATIVE NEPHRITIS IN THE RAT
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DOI:
10.1073/pnas.88.15.6560
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发表时间:
1991-08-01
影响因子:
11.1
通讯作者:
JOHNSON, RJ
JOHNSON, RJ
中科院分区:
综合性期刊1区
文献类型:
--
作者:
IIDA, H;SEIFERT, R;JOHNSON, RJ

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我们研究了血小板衍生生长因子(PDGF)或其受体(PDGF- r)是否在系膜增殖性肾小球肾炎大鼠模型中上调。疾病诱导后第3天和第5天,肾小球RNA中PDGF A链和b链mRNA均显著升高,与系膜细胞增殖时间相对应。系膜增生性肾炎患者肾小球中PDGF-R β亚基mRNA和蛋白表达均升高,在第5天达到最大。免疫染色显示表达PDGF b链的主要细胞是系膜细胞亚群;相反,大多数系膜细胞表达PDGF-R β -亚基蛋白。补体耗竭和血小板耗竭均显著降低PDGF和PDGF- r的细胞增殖和表达。因此,在系膜增生性肾炎中存在血小板和补体介导的PDGF a和B链以及PDGF- r β亚基基因转录和蛋白质合成的诱导。大部分PDGF是由系膜细胞产生的这一发现支持了PDGF在肾小球肾炎中作为自分泌生长因子的作用。
We investigated whether platelet-derived growth factor (PDGF), or its receptor (PDGF-R), was upregulated in a rat model of mesangial proliferative glomerulonephritis. A marked increase in both PDGF A- and B-chain mRNA could be demonstrated in glomerular RNA by Northern blot analysis 3 and 5 days after disease induction, corresponding to the time of mesangial cell proliferation. PDGF-R beta-subunit mRNA and protein were also increased in glomeruli in mesangial proliferative nephritis, being maximal at day 5. The principal cells expressing PDGF B-chain appeared by immunostaining to be a subpopulation of mesangial cells; in contrast, the majority of the mesangial cells expressed the PDGF-R beta-subunit protein. Both complement depletion and platelet depletion significantly reduced cell proliferation and expression of both PDGF and PDGF-R. Thus, in mesangial proliferative nephritis there is a platelet- and complement-mediated induction of PDGF A and B chain and PDGF-R beta-subunit gene transcription and protein synthesis. The finding that the majority of PDGF is produced by the mesangial cell supports the role of PDGF as an autocrine growth factor in glomerulonephritis.