Iida H, Seifert R, Alpers C E, Gronwald R G, Phillips P E, Pritzl P, Gordon K, Gown A M, Ross R, Bowen-Pope D F
Department of Medicine, University of Washington, Seattle 98195.
Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6560-4. doi: 10.1073/pnas.88.15.6560.
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.
我们研究了在系膜增生性肾小球肾炎大鼠模型中血小板衍生生长因子（PDGF）或其受体（PDGF-R）是否上调。疾病诱导后3天和5天，通过Northern印迹分析可证实在肾小球RNA中PDGF A链和B链mRNA均显著增加，这与系膜细胞增殖时间一致。在系膜增生性肾炎中，肾小球内PDGF-Rβ亚基mRNA和蛋白也增加，在第5天达到最大值。通过免疫染色显示，表达PDGF B链的主要细胞是系膜细胞的一个亚群；相反，大多数系膜细胞表达PDGF-Rβ亚基蛋白。补体耗竭和血小板耗竭均显著降低细胞增殖以及PDGF和PDGF-R的表达。因此，在系膜增生性肾炎中，存在血小板和补体介导的PDGF A链和B链以及PDGF-Rβ亚基基因转录和蛋白合成的诱导。大多数PDGF由系膜细胞产生这一发现支持了PDGF作为肾小球肾炎中自分泌生长因子的作用。
