Effects of TGF-β1 on plasminogen activation in human dental pulp cells: Role of ALK5/Smad2, TAK1 and MEK/ERK signalling

Mei-Chi Chang, Hsiao-Hua Chang, Po-Shuan Lin, Yu-An Huang, Chiu-Po Chan, Yi-Ling Tsai, Shen-Yang Lee, Po-Yuan Jeng, Han-Yueh Kuo, Sin-Yuet Yeung, Jiiang-Huei Jeng

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Abstract

Transforming growth factor-β1 (TGF-β1) plays an important role in the pulpal repair and dentinogenesis. Plasminogen activation (PA) system regulates extracellular matrix turnover. In this study, we investigated the effects of TGF-β1 on PA system of dental pulp cells and its signalling pathways. Dental pulp cells were treated with different concentrations of TGF-β1. MTT assay, reverse transcription-polymerase chain reaction, Western blotting and enzyme-linked immunosorbant assay (ELISA) were used to detect the effect of TGF-β1 on cell viability, mRNA and protein expression of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1) as well as their secretion. The phosphorylation of Smad2 and TAK1 was analysed by Pathscan ELISA or Western blotting. Cells were pretreated with SB431542 (ALK5/Smad2/3 inhibitor), 5z-7-oxozeaenol (TAK1 inhibitor) and U0126 (MEK/ERK inhibitor) for examining the related signalling. TGF-β1 slightly inhibited cell growth that was reversed by SB431542. TGF-β1 upregulated both RNA and protein expression of PAI-1 and uPAR, whereas it downregulated uPA expression. Accordingly, TGF-β1 stimulated PAI-1 and soluble uPAR (suPAR) secretion of pulp cells, whereas uPA secretion was inhibited. TGF-β1 induced the phosphorylation of Smad2 and TAK1. In addition, SB431542, 5z-7-oxozeaenol and U0126 attenuated the TGF-β1-induced secretion of PAI-1 and suPAR. These results indicate that TGF-β1 is possibly involved in the repair/regeneration and inflammatory processes of dental pulp via regulation of PAI-1, uPA and uPAR. These effects of TGF-β1 are related to activation of ALK5/Smad2, TAK1 and MEK/ERK signalling pathways. Clarifying the signal transduction for the effects of TGF-β1 is helpful for pulpo-dentin regeneration and tissue engineering. Copyright © 2016 John Wiley & Sons, Ltd.

Original languageEnglish
Pages (from-to)854-863
Number of pages10
JournalJournal of Tissue Engineering and Regenerative Medicine
Volume12
Issue number4
DOIs
Publication statusPublished - Apr 2018

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Dental Pulp
Plasminogen
Mitogen-Activated Protein Kinase Kinases
Transforming Growth Factors
Pulp
Chemical activation
Plasminogen Activator Inhibitor 1
Urokinase-Type Plasminogen Activator
Urokinase Plasminogen Activator Receptors
Assays
Phosphorylation
Intercellular Signaling Peptides and Proteins
Regeneration
Repair
Dentinogenesis
Enzymes
Western Blotting
Proteins
Signal transduction
MAP Kinase Signaling System

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Effects of TGF-β1 on plasminogen activation in human dental pulp cells : Role of ALK5/Smad2, TAK1 and MEK/ERK signalling. / Chang, Mei-Chi; Chang, Hsiao-Hua; Lin, Po-Shuan; Huang, Yu-An; Chan, Chiu-Po; Tsai, Yi-Ling; Lee, Shen-Yang; Jeng, Po-Yuan; Kuo, Han-Yueh; Yeung, Sin-Yuet; Jeng, Jiiang-Huei.

In: Journal of Tissue Engineering and Regenerative Medicine, Vol. 12, No. 4, 04.2018, p. 854-863.

Research output: Contribution to journalArticle

Chang, M-C, Chang, H-H, Lin, P-S, Huang, Y-A, Chan, C-P, Tsai, Y-L, Lee, S-Y, Jeng, P-Y, Kuo, H-Y, Yeung, S-Y & Jeng, J-H 2018, 'Effects of TGF-β1 on plasminogen activation in human dental pulp cells: Role of ALK5/Smad2, TAK1 and MEK/ERK signalling', Journal of Tissue Engineering and Regenerative Medicine, vol. 12, no. 4, pp. 854-863. https://doi.org/10.1002/term.2339
Chang, Mei-Chi ; Chang, Hsiao-Hua ; Lin, Po-Shuan ; Huang, Yu-An ; Chan, Chiu-Po ; Tsai, Yi-Ling ; Lee, Shen-Yang ; Jeng, Po-Yuan ; Kuo, Han-Yueh ; Yeung, Sin-Yuet ; Jeng, Jiiang-Huei. / Effects of TGF-β1 on plasminogen activation in human dental pulp cells : Role of ALK5/Smad2, TAK1 and MEK/ERK signalling. In: Journal of Tissue Engineering and Regenerative Medicine. 2018 ; Vol. 12, No. 4. pp. 854-863.
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abstract = "Transforming growth factor-β1 (TGF-β1) plays an important role in the pulpal repair and dentinogenesis. Plasminogen activation (PA) system regulates extracellular matrix turnover. In this study, we investigated the effects of TGF-β1 on PA system of dental pulp cells and its signalling pathways. Dental pulp cells were treated with different concentrations of TGF-β1. MTT assay, reverse transcription-polymerase chain reaction, Western blotting and enzyme-linked immunosorbant assay (ELISA) were used to detect the effect of TGF-β1 on cell viability, mRNA and protein expression of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1) as well as their secretion. The phosphorylation of Smad2 and TAK1 was analysed by Pathscan ELISA or Western blotting. Cells were pretreated with SB431542 (ALK5/Smad2/3 inhibitor), 5z-7-oxozeaenol (TAK1 inhibitor) and U0126 (MEK/ERK inhibitor) for examining the related signalling. TGF-β1 slightly inhibited cell growth that was reversed by SB431542. TGF-β1 upregulated both RNA and protein expression of PAI-1 and uPAR, whereas it downregulated uPA expression. Accordingly, TGF-β1 stimulated PAI-1 and soluble uPAR (suPAR) secretion of pulp cells, whereas uPA secretion was inhibited. TGF-β1 induced the phosphorylation of Smad2 and TAK1. In addition, SB431542, 5z-7-oxozeaenol and U0126 attenuated the TGF-β1-induced secretion of PAI-1 and suPAR. These results indicate that TGF-β1 is possibly involved in the repair/regeneration and inflammatory processes of dental pulp via regulation of PAI-1, uPA and uPAR. These effects of TGF-β1 are related to activation of ALK5/Smad2, TAK1 and MEK/ERK signalling pathways. Clarifying the signal transduction for the effects of TGF-β1 is helpful for pulpo-dentin regeneration and tissue engineering. Copyright {\circledC} 2016 John Wiley & Sons, Ltd.",
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AU - Chan, Chiu-Po

AU - Tsai, Yi-Ling

AU - Lee, Shen-Yang

AU - Jeng, Po-Yuan

AU - Kuo, Han-Yueh

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