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转化生长因子-β刺激培养的大鼠系膜细胞增殖:血小板衍生生长因子β受体表达的作用

TGF-beta stimulates rat mesangial cell proliferation in culture: role of PDGF beta-receptor expression.

作者信息

Haberstroh U, Zahner G, Disser M, Thaiss F, Wolf G, Stahl R A

机构信息

Department of Medicine, University of Frankfurt, Federal Republic of Germany.

出版信息

Am J Physiol. 1993 Feb;264(2 Pt 2):F199-205. doi: 10.1152/ajprenal.1993.264.2.F199.

DOI:10.1152/ajprenal.1993.264.2.F199
PMID:8447432
Abstract

Transforming growth factor (TGF)-beta is known to increase mesangial cell (MC) matrix; however, its possible role on MC proliferation is controversial. We therefore studied the influence of TGF-beta on MC proliferation in culture and evaluated its effect on the platelet-derived growth factor (PDGF) B-chain as well as the expression of the PDGF beta-receptor. TGF-beta (1 ng/ml) increases MC DNA synthesis by approximately threefold after 48 h of incubation. TGF-beta-induced MC proliferation was also confirmed by cell counts. A neutralizing anti-TGF-beta antibody completely blocked this growth promoting activity. The levels of PDGF beta-receptor steady-state mRNA were increased by TGF-beta at 48 h. This was associated with an increase in receptor density per cell as measured by receptor kinetic studies. PDGF B-chain mRNA was also increased by TGF-beta at 48 h. A neutralizing anti-PDGF B-antibody causes no reduction of TGF-beta-induced DNA synthesis; however, suramin completely inhibited the mitogenic effect of TGF-beta. We conclude that TGF-beta stimulates MC growth in long-term culture, a process in which upregulation of the PDGF beta-receptor and enhanced synthesis of PDGF B-chain might be involved.

摘要

已知转化生长因子(TGF)-β可增加系膜细胞(MC)基质;然而,其对MC增殖的可能作用存在争议。因此,我们研究了TGF-β对培养的MC增殖的影响,并评估了其对血小板衍生生长因子(PDGF)B链以及PDGFβ受体表达的作用。孵育48小时后,TGF-β(1纳克/毫升)可使MC的DNA合成增加约三倍。通过细胞计数也证实了TGF-β诱导的MC增殖。一种中和性抗TGF-β抗体完全阻断了这种促生长活性。48小时时,TGF-β可增加PDGFβ受体稳态mRNA的水平。通过受体动力学研究测量,这与每个细胞受体密度的增加相关。48小时时,TGF-β也可增加PDGF B链mRNA。一种中和性抗PDGF B抗体不会降低TGF-β诱导的DNA合成;然而,苏拉明完全抑制了TGF-β的促有丝分裂作用。我们得出结论,TGF-β在长期培养中刺激MC生长,这一过程可能涉及PDGFβ受体的上调和PDGF B链合成的增强。

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