[血小板衍生生长因子-BB通过转化生长因子-β信号系统部分抑制血管平滑肌细胞中p21（WAF1）的表达]

[Platelet-derived growth factor-BB inhibited p21(WAF1) expression partially through transforming growth factor-beta signalling system in vascular smooth muscle cell].

作者信息

Pan Da-Bin, Ke Yong-Sheng, Liu Wen-Jie, Wei You-Quan, Tang Jun, Cao Heng

机构信息

Department of Cardiology, Affiliated Yijishan Hospital of Wannan Medical College, Wuhu 241001, China.

出版信息

Zhonghua Xin Xue Guan Bing Za Zhi. 2010 Feb;38(2):160-5.

PMID:20398565

Abstract

OBJECTIVE

To assess if the modulating effect of platelet-derived growth factor (PDGF)-BB on p21(WAF1) was mediated by upregulating transforming growth factor (TGF)-beta(1) expression in vascular smooth muscle cells (VSMC).

METHODS

TGF-beta(1) mRNA and protein expressions were measured by reverse transcription-PCR and ELISA, the protein expressions of p21(WAF1) and the downstream TGF-beta signalling including TGF-beta type I receptor (ALK-5 in VSMC), Smurf2, pSmad2/3, Smad4, Smad7 were detected by Western blot.

RESULTS

PDGF-BB significantly upregulated the expressions of TGF-beta(1) at mRNA (0.79-fold) and protein (1.98-fold) levels in VSMC, significantly inhibited the expression of p21(WAF1) (-67 +/- 12)%, and enhanced the expressions of ALK-5, pSmad2/3, Smad4, Smurf2 protein by 1.21-fold, 0.95-fold, 0.69-fold and 2.55-fold respectively, inhibited Smad7 expression (-65 +/- 9)%, these alterations were partially restored by anti-TGF-beta(1) neutralizing antibody.

CONCLUSIONS

These findings suggested that PDGF-BB inhibited p21(WAF1) expression in VSMC partially through upregulating TGF-beta(1) expression via PDGF-BB and TGF-beta signalling pathways.

摘要

目的

评估血小板衍生生长因子（PDGF）-BB对p21（WAF1）的调节作用是否通过上调血管平滑肌细胞（VSMC）中转化生长因子（TGF）-β1的表达来介导。

方法

采用逆转录-PCR和ELISA检测TGF-β1 mRNA和蛋白表达，通过蛋白质印迹法检测p21（WAF1）及下游TGF-β信号通路相关蛋白表达，包括VSMC中的TGF-βⅠ型受体（ALK-5）、Smurf2、磷酸化Smad2/3、Smad4、Smad7。

结果

PDGF-BB显著上调VSMC中TGF-β1的mRNA（0.79倍）和蛋白（1.98倍）表达，显著抑制p21（WAF1）的表达（-67±12）%，使ALK-5、磷酸化Smad2/3、Smad4、Smurf2蛋白表达分别增强1.21倍、0.95倍、0.69倍和2.55倍，抑制Smad7表达（-65±9）%，抗TGF-β1中和抗体可部分逆转这些变化。