Abstract

Lung fibroblasts play critical roles in fibrotic procedures and contribute to lung fibrosis. Several studies indicated that thrombin, a disintegrin and metalloproteinase 17 (ADAM17), and connective tissue growth factor (CTGF) participate in the formation of pulmonary fibrosis. In this study, we examined the involvement of the ADAM17/epidermal growth factor receptor (EGFR)/extracellular signal-regulated kinase (ERK) pathway in thrombin-stimulated CTGF manifestation in human lung fibroblasts (WI-38). We found that cells treated with thrombin significantly increased ADAM17 expression, ADAM17 and c-Jun phosphorylation in time-dependent manners. Thrombin-stimulated CTGF expression, ERK and c-Jun phosphorylation were inhibited by TAPI-0 (an ADAM17 inhibitor). Moreover, U0126 (an ERK inhibitor) inhibited thrombin-stimulated CTGF expression and c-Jun phosphorylation. Cells transfected with small interfering RNA of the EGFR attenuated thrombin-stimulated ERK phosphorylation, c-Jun phosphorylation, and CTGF expression. Thus, these results suggested that ADAM17/EGFR-dependent ERK activation mediated thrombin-stimulated CTGF expression in human lung fibroblasts.

LanguageEnglish
Pages39-45
Number of pages7
JournalExperimental Cell Research
Volume370
Issue number1
DOIs
Publication statusPublished - Sep 1 2018

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Connective Tissue Growth Factor
Disintegrins
Extracellular Signal-Regulated MAP Kinases
Metalloproteases
Epidermal Growth Factor Receptor
Thrombin
Fibroblasts
Lung
Phosphorylation
Pulmonary Fibrosis
Small Interfering RNA
Fibrosis

Keywords

  • CTGF
  • EGFR
  • ERK
  • Lung fibroblasts
  • Thrombin

ASJC Scopus subject areas

  • Cell Biology

Cite this

ADAM17/EGFR-dependent ERK activation mediates thrombin-induced CTGF expression in human lung fibroblasts. / Chen, Hui Yu; Lin, Chien Huang; Chen, Bing Chang.

In: Experimental Cell Research, Vol. 370, No. 1, 01.09.2018, p. 39-45.

Research output: Contribution to journalArticle

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N2 - Lung fibroblasts play critical roles in fibrotic procedures and contribute to lung fibrosis. Several studies indicated that thrombin, a disintegrin and metalloproteinase 17 (ADAM17), and connective tissue growth factor (CTGF) participate in the formation of pulmonary fibrosis. In this study, we examined the involvement of the ADAM17/epidermal growth factor receptor (EGFR)/extracellular signal-regulated kinase (ERK) pathway in thrombin-stimulated CTGF manifestation in human lung fibroblasts (WI-38). We found that cells treated with thrombin significantly increased ADAM17 expression, ADAM17 and c-Jun phosphorylation in time-dependent manners. Thrombin-stimulated CTGF expression, ERK and c-Jun phosphorylation were inhibited by TAPI-0 (an ADAM17 inhibitor). Moreover, U0126 (an ERK inhibitor) inhibited thrombin-stimulated CTGF expression and c-Jun phosphorylation. Cells transfected with small interfering RNA of the EGFR attenuated thrombin-stimulated ERK phosphorylation, c-Jun phosphorylation, and CTGF expression. Thus, these results suggested that ADAM17/EGFR-dependent ERK activation mediated thrombin-stimulated CTGF expression in human lung fibroblasts.

AB - Lung fibroblasts play critical roles in fibrotic procedures and contribute to lung fibrosis. Several studies indicated that thrombin, a disintegrin and metalloproteinase 17 (ADAM17), and connective tissue growth factor (CTGF) participate in the formation of pulmonary fibrosis. In this study, we examined the involvement of the ADAM17/epidermal growth factor receptor (EGFR)/extracellular signal-regulated kinase (ERK) pathway in thrombin-stimulated CTGF manifestation in human lung fibroblasts (WI-38). We found that cells treated with thrombin significantly increased ADAM17 expression, ADAM17 and c-Jun phosphorylation in time-dependent manners. Thrombin-stimulated CTGF expression, ERK and c-Jun phosphorylation were inhibited by TAPI-0 (an ADAM17 inhibitor). Moreover, U0126 (an ERK inhibitor) inhibited thrombin-stimulated CTGF expression and c-Jun phosphorylation. Cells transfected with small interfering RNA of the EGFR attenuated thrombin-stimulated ERK phosphorylation, c-Jun phosphorylation, and CTGF expression. Thus, these results suggested that ADAM17/EGFR-dependent ERK activation mediated thrombin-stimulated CTGF expression in human lung fibroblasts.

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