Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Public Health, Department of Cardiology, Qilu Hospital of Shandong University, Ji'nan 250012, PR China.
Int J Biochem Cell Biol. 2012 Jun;44(6):1031-9. doi: 10.1016/j.biocel.2012.03.013. Epub 2012 Mar 29.
Accumulation of collagen I and III in the myocardium is a prominent feature of interstitial fibrosis. Prostaglandin F(2α) (PGF(2α)) facilitates fibrosis by increasing collagen synthesis. However, the underlying mechanisms mediating the effect of PGF(2α) on collagen expression in cardiac fibroblasts are not yet fully elucidated. We measured the mRNA and protein levels of collagen I and III by quantitative real-time PCR and ELISA, respectively. Activation of signaling pathways was determined by western blot analysis. In primary rat cardiac fibroblasts, treatment with PGF(2α) stimulated both the mRNA and protein levels of collagen I and III, and pretreatment with the F-prostanoid (FP) receptor antagonist AL-8810, protein kinase C inhibitor LY-333531, and Rho kinase inhibitor Y-27632 significantly inhibited PGF(2α)-induced collagen I and III expression. FP receptor, protein kinase C, and Rho kinase were activated with PGF(2α) treatment. PGF(2α) may be an important regulator in the synthesis of collagen I and III via an FP receptor/protein kinase C/Rho kinase cascade in cardiac fibroblasts, which might be a new therapeutic target for myocardial fibrosis.
胶原 I 和 III 在心肌中的积累是间质纤维化的一个突出特征。前列腺素 F2α（PGF2α）通过增加胶原合成促进纤维化。然而，介导 PGF2α 对心肌成纤维细胞胶原表达影响的潜在机制尚未完全阐明。我们通过实时定量 PCR 和 ELISA 分别测量了胶原 I 和 III 的 mRNA 和蛋白水平。通过 Western blot 分析测定信号通路的激活。在原代大鼠心肌成纤维细胞中，PGF2α 处理刺激胶原 I 和 III 的 mRNA 和蛋白水平，而 FP 受体拮抗剂 AL-8810、蛋白激酶 C 抑制剂 LY-333531 和 Rho 激酶抑制剂 Y-27632 的预处理显著抑制 PGF2α 诱导的胶原 I 和 III 表达。FP 受体、蛋白激酶 C 和 Rho 激酶在 PGF2α 处理下被激活。PGF2α 可能通过心肌成纤维细胞中的 FP 受体/蛋白激酶 C/Rho 激酶级联反应成为胶原 I 和 III 合成的重要调节剂，这可能成为心肌纤维化的一个新的治疗靶点。
