Connective tissue growth factor (CTGF) is a cysteine-rich protein induced by transforming growth factor beta (TGF- beta) in connective tissue cells. CTGF can trigger many of the cellular processes underlying fibrosis, such as cell proliferation, adhesion, migration and the synthesis of extracellular matrix; however, its role in acute and chronic cardiac injury is not fully understood. Here, we show that TGF- beta is a specific inducer of CTGF expression in both cardiac fibroblasts and cardiac myocytes. The activity of a CTGF promoter-based reporter construct correlated with endogenous CTGF expression, suggesting that TGF- beta induces CTGF expression most likely by activating its promoter. Upregulation of CTGF coincided with an increase in fibronectin, collagen type I and plasminogen activator inhibitor-1 production. Forskolin, a stimulator of cyclic AMP, blocked TGF- beta induced CTGF expression and reduced the basal level of CTGF, whereas an inhibitor that blocks the MAP kinase signaling pathway (PD 98059) significantly enhanced TGF- beta induced CTGF expression. Furthermore, we found that both TGF- beta and CTGF mRNAs were significantly elevated in the left ventricles and septa of rat hearts 2-16 weeks following myocardial infarction. This correlated well with concomitant increases in fibronectin, and type I and type III collagen mRNA levels in these animal hearts. Significant upregulation of CTGF was also detected in human heart samples derived from patients diagnosed with cardiac ischemia. Based on these findings, we propose that CTGF is an important mediator of TGF- beta signaling in the heart and abnormal expression of this gene could be used as a diagnostic marker for cardiac fibrosis.

中文翻译：

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TGF-β在心脏成纤维细胞和心肌细胞中诱导CTGF表达：在心脏纤维化中的潜在作用。

结缔组织生长因子（CTGF）是通过在结缔组织细胞中转化生长因子β（TGF-β）诱导的富含半胱氨酸的蛋白质。CTGF可以触发许多纤维化的细胞过程，例如细胞增殖，粘附，迁移和细胞外基质的合成。然而，其在急性和慢性心脏损伤中的作用尚不完全清楚。在这里，我们显示TGF-β是心脏成纤维细胞和心肌细胞中CTGF表达的特异性诱导剂。基于CTGF启动子的报告基因构建物的活性与内源性CTGF表达相关，这表明TGF-β最有可能通过激活其启动子来诱导CTGF表达。CTGF的上调与纤连蛋白，I型胶原和纤溶酶原激活物抑制剂1产生的增加同时发生。福斯科林，环AMP的刺激剂阻断TGF-β诱导的CTGF表达并降低CTGF的基础水平，而阻断MAP激酶信号通路的抑制剂（PD 98059）则显着增强TGF-β诱导的CTGF表达。此外，我们发现心肌梗塞后2-16周，大鼠心脏左心室和隔中的TGF-β和CTGF mRNA均显着升高。这与这些动物心脏中纤连蛋白以及I型和III型胶原mRNA水平的随之增加密切相关。在被诊断出患有心脏缺血的患者的人心脏样本中也检测到了CTGF的显着上调。根据这些发现，