TGF-β Induced CTGF Expression in Human Lung Epithelial Cells through ERK, ADAM17, RSK1, and C/EBPβ Pathways.
TGF-β Induced CTGF Expression in Human Lung Epithelial Cells through ERK, ADAM17, RSK1, and C/EBPβ Pathways.
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TGF-β通过ERK，ADAM17，RSK1和C/EBPβ途径在人肺上皮细胞中诱导CTGF表达。
DOI：
10.3390/ijms21239084
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发表时间：
2020-11-29
影响因子：
5.6
通讯作者：
Chen BC
中科院分区：
文献类型：
--
作者：
Ou SC;Bai KJ;Cheng WH;Chen JY;Lin CH;Wen HC;Chen BC
背景：肺上皮细胞在特发性肺纤维化中起关键作用。研究方法：在本研究中，我们研究了细胞外信号调节激酶（ERK）/a去整合素和金属蛋白酶17（ADAM 17）/核糖体S6激酶1（RSK 1）/CCAAT/增强子结合蛋白β（C/EBPβ）信号通路是否调节转化生长因子-β（TGF-β）诱导的人肺上皮细胞（A549）结缔组织生长因子（CTGF）表达。结果如下：我们的研究结果显示，ADAM 17 siRNA、TAPI-0、ERK抑制剂U 0126、RSK 1 siRNA和C/EBPβ siRNA均能减弱TGF-β诱导的CTGF表达。U 0126可减弱TGF-β诱导的ERK磷酸化以及ADAM 17磷酸化。TAPI-0和U 0126可抑制TGF-β诱导的RSK 1磷酸化增加。U 0126、ADAM 17 siRNA和RSK 1 siRNA可减弱TGF-β诱导的C/EBPβ磷酸化。此外，TGF-β增加了C/EBPβ向CTGF启动子的募集。此外，TGF-β增强了纤维连接蛋白（FN）（一种上皮-间充质转化（EMT）标志物）和CTGF mRNA水平，并降低了E-钙粘蛋白mRNA水平。此外，ADAM 17 siRNA和CTGF siRNA可降低TGF-β刺激的FN蛋白表达。结论：TGF-β通过ERK/ADAM 17/RSK 1/C/EBPβ信号通路诱导CTGF表达。此外，ADAM 17和CTGF参与TGF-β诱导的人肺上皮细胞FN表达。
Background: Lung epithelial cells play critical roles in idiopathic pulmonary fibrosis. Methods: In the present study, we investigated whether transforming growth factor-β (TGF-β)-induced expression of connective tissue growth factor (CTGF) was regulated by the extracellular signal-regulated kinase (ERK)/a disintegrin and metalloproteinase 17 (ADAM17)/ribosomal S6 kinases 1 (RSK1)/CCAAT/enhancer-binding protein β (C/EBPβ) signaling pathway in human lung epithelial cells (A549). Results: Our results revealed that TGF-β-induced CTGF expression was weakened by ADAM17 small interfering RNA (ADAM17 siRNA), TNF-α processing inhibitor-0 (TAPI-0, an ADAM17 inhibitor), U0126 (an ERK inhibitor), RSK1 siRNA, and C/EBPβ siRNA. TGF-β-induced ERK phosphorylation as well as ADAM17 phosphorylation was attenuated by U0126. The TGF-β-induced increase in RSK1 phosphorylation was inhibited by TAPI-0 and U0126. TGF-β-induced C/EBPβ phosphorylation was weakened by U0126, ADAM17 siRNA, and RSK1 siRNA. In addition, TGF-β increased the recruitment of C/EBPβ to the CTGF promoter. Furthermore, TGF-β enhanced fibronectin (FN), an epithelial–mesenchymal transition (EMT) marker, and CTGF mRNA levels and reduced E-cadherin mRNA levels. Moreover, TGF-β-stimulated FN protein expression was reduced by ADAM17 siRNA and CTGF siRNA. Conclusion: The results suggested that TGF-β induces CTGF expression through the ERK/ADAM17/RSK1/C/EBPβ signaling pathway. Moreover, ADAM17 and CTGF participate in TGF-β-induced FN expression in human lung epithelial cells.
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DOI：
10.1016/j.bbadis.2013.03.001
发表时间：
2013-07
影响因子：
6.2
作者：
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通讯作者：
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