Micke Patrick, Hackbusch Daniel, Mercan Sibel, Stawowy Philipp, Tsuprykov Oleg, Unger Thomas, Ostman Arne, Kappert Kai
Cancer Centrum Karolinska, Department of Oncology-Pathology, Karolinska Institute, Stockholm, Sweden.
Biochem Biophys Res Commun. 2009 May 15;382(4):678-84. doi: 10.1016/j.bbrc.2009.03.078. Epub 2009 Mar 18.
Protein tyrosine phosphatases (PTPs) are regulators of growth factor signalling in vascular remodelling. The aim of this study was to evaluate PTP expression in the context of PDGF-signalling in the adventitia after angioplasty. Utilising a rat carotid artery model, the adventitial layers of injured and non-injured vessels were laser microdissected. The mRNA expression of the PDGF beta-receptor, the ligands PDGF-A/B/C/D and the receptor-antagonising PTPs (DEP-1, TC-PTP, SHP-2, PTP1B) were determined and correlated to vascular morphometrics, proliferation markers and PDGF beta-receptor phosphorylation. The levels of the PDGF beta-receptor, PDGF-C and PDGF-D were upregulated concurrently with the antagonising PTPs DEP-1 and TC-PTP at day 8, and normalised at day 14 after vessel injury. Although the proliferation parameters were time-dependently altered in the adventitial layer, the phosphorylation of the PDGF beta-receptor remained unchanged. The expression dynamics of specific PTPs indicate a regulatory role of PDGF-signalling also in the adventitia during vascular remodelling.
蛋白酪氨酸磷酸酶(PTPs)是血管重塑过程中生长因子信号传导的调节因子。本研究的目的是评估血管成形术后外膜中血小板源性生长因子(PDGF)信号传导背景下PTP的表达情况。利用大鼠颈动脉模型,对损伤和未损伤血管的外膜层进行激光显微切割。测定了PDGFβ受体、配体PDGF-A/B/C/D以及受体拮抗型PTPs(DEP-1、TC-PTP、SHP-2、PTP1B)的mRNA表达,并将其与血管形态学、增殖标志物以及PDGFβ受体磷酸化进行关联分析。在血管损伤后第8天,PDGFβ受体、PDGF-C和PDGF-D的水平与拮抗型PTPs DEP-1和TC-PTP同时上调,并于第14天恢复正常。尽管外膜层的增殖参数随时间发生变化,但PDGFβ受体的磷酸化水平保持不变。特定PTPs的表达动态表明,在血管重塑过程中,PDGF信号传导在外膜中也发挥着调节作用。