TGF-ß Induced CTGF Expression in Human Lung Epithelial Cells through ERK, ADAM17, RSK1, and C/EBPß Pathways.
Int J Mol Sci
; 21(23)2020 Nov 29.
Article
em En
| MEDLINE
| ID: mdl-33260349
ABSTRACT
BACKGROUND:
Lung epithelial cells play critical roles in idiopathic pulmonary fibrosis.METHODS:
In the present study, we investigated whether transforming growth factor-ß (TGF-ß)-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 ß (C/EBPß) signaling pathway in human lung epithelial cells (A549).RESULTS:
Our results revealed that TGF-ß-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/EBPß siRNA. TGF-ß-induced ERK phosphorylation as well as ADAM17 phosphorylation was attenuated by U0126. The TGF-ß-induced increase in RSK1 phosphorylation was inhibited by TAPI-0 and U0126. TGF-ß-induced C/EBPß phosphorylation was weakened by U0126, ADAM17 siRNA, and RSK1 siRNA. In addition, TGF-ß increased the recruitment of C/EBPß to the CTGF promoter. Furthermore, TGF-ß enhanced fibronectin (FN), an epithelial-mesenchymal transition (EMT) marker, and CTGF mRNA levels and reduced E-cadherin mRNA levels. Moreover, TGF-ß-stimulated FN protein expression was reduced by ADAM17 siRNA and CTGF siRNA.CONCLUSION:
The results suggested that TGF-ß induces CTGF expression through the ERK/ADAM17/RSK1/C/EBPß signaling pathway. Moreover, ADAM17 and CTGF participate in TGF-ß-induced FN expression in human lung epithelial cells.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Fator de Crescimento Transformador beta
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Proteína beta Intensificadora de Ligação a CCAAT
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Proteínas Quinases S6 Ribossômicas 90-kDa
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MAP Quinases Reguladas por Sinal Extracelular
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Células Epiteliais
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Fator de Crescimento do Tecido Conjuntivo
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Proteína ADAM17
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Pulmão
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article