Sharma H S, van Heugten H A, Goedbloed M A, Verdouw P D, Lamers J M
Department of Experimental Cardiology (Thoraxcenter), Faculty of Medicine and Health Sciences, Erasmus University, Rotterdam, The Netherlands.
Biochem Biophys Res Commun. 1994 Nov 30;205(1):105-12. doi: 10.1006/bbrc.1994.2636.
Angiotensin II (ANG II), a potent vasoconstricting peptide, may act as a growth factor for cardiac muscle cells and induce hypertrophy. We examined the molecular phenotype of neonatal rat cardiac fibroblasts in relation to ANG II by studying the expression pattern of three transcription factors (Egr-1, c-fos and c-jun) and the transforming growth factor-beta 1 (TGF-beta 1). ANG II did not affect cell proliferation and growth of serum deprived neonatal cardiac fibroblasts as predicted from their DNA and protein contents. The expression of Egr-1 and c-fos was induced as early as 15 min that reached maximal levels at 45 min and declined thereafter, whereas c-jun was induced at 45 min and remained elevated up to 2 hrs of ANG II addition. ANG II up-regulated the expression of TGF-beta 1, which became apparent after 1 hr of incubation and reached a plateau between 16-48 hrs. Our results indicate that ANG II transiently stimulates the expression of transcription factors, which may up-regulate TGF-beta 1, that in turn could contribute to the process of myocardial extra-cellular matrix remodeling in hypertrophy.
血管紧张素II（ANG II）是一种有效的血管收缩肽，可能作为心肌细胞的生长因子并诱导肥大。我们通过研究三种转录因子（Egr-1、c-fos和c-jun）以及转化生长因子-β1（TGF-β1）的表达模式，来检测新生大鼠心脏成纤维细胞与ANG II相关的分子表型。如根据其DNA和蛋白质含量所预测的那样，ANG II并不影响血清剥夺的新生心脏成纤维细胞的细胞增殖和生长。Egr-1和c-fos的表达早在15分钟时就被诱导，在45分钟时达到最高水平，此后下降，而c-jun在45分钟时被诱导，并在添加ANG II后长达2小时保持升高。ANG II上调了TGF-β1的表达，这在孵育1小时后变得明显，并在16 - 48小时之间达到平台期。我们的结果表明，ANG II短暂刺激转录因子的表达，这可能上调TGF-β1，进而可能有助于肥大过程中心肌细胞外基质重塑的进程。
