Regulation of serum-induced fibronectin expression by protein kinases, cytoskeletal integrity, and CREB
Regulation of serum-induced fibronectin expression by protein kinases, cytoskeletal integrity, and CREB
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DOI：
10.1152/ajplung.00445.2000
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发表时间：
2002-02-01
影响因子：
4.9
通讯作者：
Roman, J
中科院分区：
文献类型：
--
作者：
Michaelson, JE;Ritzenthaler, JD;Roman, J
肺损伤，其特征在于与血清蛋白质的间质和肺泡空间的洪水，诱导纤维连接蛋白（FN）的表达。这种细胞粘附性细胞外基质（ECM）糖蛋白被认为调节炎症和伤口修复。小鼠NIH/3 T3成纤维细胞转染1.2 kb的人FN启动子报告基因进行了研究，以深入了解FN的诱导血清参与的机制。FN基因的转录，随后FN蛋白的生产，增强了10%的胎牛血清。蛋白激酶C和丝裂原活化蛋白激酶抑制剂可阻断这种作用。ECM通常存在于受损组织中（即，I型胶原、纤维蛋白和FN）没有影响。相反，破坏肌动蛋白微丝抑制，而破坏微管组装增强，血清诱导的FN反应。血清和微管破坏对FN基因转录的刺激作用与转录因子cAMP反应元件结合蛋白的DNA结合增加有关。这些数据表明，调节血清诱导的FN在成纤维细胞中的表达是依赖于蛋白激酶和细胞骨架的完整性。
Lung injury, characterized by the flooding of interstitial and alveolar spaces with serum proteins, induces the expression of fibronectin (FN). This cell-adhesive extracellular matrix (ECM) glycoprotein is believed to modulate inflammation and wound repair. Murine NIH/3T3 fibroblasts transfected with a 1.2-kb human FN promoter-reporter gene were studied to gain insight into the mechanisms involved in the induction of FN by serum. Transcription of the FN gene, followed by FN protein production, was enhanced by 10% fetal bovine serum. This effect was blocked by inhibitors of protein kinase C and mitogen-activated protein kinases. ECMs typically found in injured tissues (i.e., type I collagen, fibrin, and FN) had no effect. Conversely, disruption of actin microfilaments inhibited, whereas disruption of microtubular assembly enhanced, the serum-induced FN response. The stimulatory effects of serum and microtubular disruption on FN gene transcription were related to increased DNA binding of the transcription factor cAMP response element binding protein. The data suggest that regulation of serum-induced FN expression in fibroblasts is dependent on protein kinases and on cytoskeletal integrity.