Department of Cardiology, Qingdao Municipal Hospital, Qingdao, Shandong, Peoples Republic of China.
Cell Biol Int. 2011 Feb;35(2):93-8. doi: 10.1042/CBI20090104.
U2 (urotensin-2) is the most potent vasoconstrictor in mammals which is involved in cardiac remodelling, including cardiac hypertrophy and cardiac fibrosis. Although the cellular mechanisms of the U2-induced vasoconstriction have been extensively studied, the signalling pathways involved in U2-induced TGF-β1 (transforming growth factor-β1) expression and collagen synthesis remain unclear. In this study, we show that U2 promoted collagen synthesis and ERK1/2 (extracellular signal-regulated kinase 1/2) activation in neonatal cardiac fibroblasts. The U2-induced collagen synthesis and TGF-β1 production were significantly but not completely inhibited by blocking ERK1/2. Both ERK1/2 inhibitor and TGF-β1 antibody could separately inhibit U2-induced collagen synthesis, and the synergistic inhibition effect was observed by blocking ERK1/2 and TGF-β1 simultaneously. These data suggest that U2 promotes collagen synthesis via ERK1/2-dependent and independent TGF-β1 pathway in neonatal cardiac fibroblasts.
U2（尿促素-2）是哺乳动物中最强的血管收缩剂，参与心脏重构，包括心肌肥厚和心肌纤维化。尽管 U2 诱导的血管收缩的细胞机制已经得到广泛研究，但 U2 诱导 TGF-β1（转化生长因子-β1）表达和胶原合成的信号通路仍不清楚。在本研究中，我们发现 U2 促进了新生心肌成纤维细胞的胶原合成和 ERK1/2（细胞外信号调节激酶 1/2）的激活。ERK1/2 阻断剂可显著但不完全抑制 U2 诱导的胶原合成和 TGF-β1 的产生。ERK1/2 抑制剂和 TGF-β1 抗体均可单独抑制 U2 诱导的胶原合成，同时阻断 ERK1/2 和 TGF-β1 可观察到协同抑制作用。这些数据表明，U2 通过 ERK1/2 依赖和独立的 TGF-β1 途径促进新生心肌成纤维细胞的胶原合成。
