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Effects of transforming growth factor‐β1 on plasminogen activation in stem cells from the apical papilla: role of activating receptor‐like kinase 5/Smad2 and mitogen‐activated protein kinase kinase (MEK)/extracellular signal‐regulated kinase (ERK) signalling
Author(s) -
Chang M. C.,
Chang H. H.,
Hsieh W. C.,
Huang W. L.,
Lian Y. C.,
Jeng P. Y.,
Wang Y. L.,
Yeung S. Y.,
Jeng J. H.
Publication year - 2020
Publication title -
international endodontic journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.988
H-Index - 119
eISSN - 1365-2591
pISSN - 0143-2885
DOI - 10.1111/iej.13266
Subject(s) - urokinase receptor , mapk/erk pathway , mek inhibitor , plasminogen activator , plasminogen activator inhibitor 1 , kinase , transforming growth factor , chemistry , protein kinase a , microbiology and biotechnology , biology , endocrinology
Aim To study the effects of TGF‐β1 on the plasminogen activation (PA) system of stem cells from the apical papilla (SCAP) and its signalling. Methodology SCAP cells were isolated from the apical papilla of immature permanent teeth extracted for orthodontic reasons. They were exposed to various concentration of TGF‐β1 with/without pretreatment and coincubation by SB431542 (ALK/Smad2/3 inhibitor), or U0126 (MEK/ERK inhibitor). MTT assay, Western blotting and enzyme‐linked immunosorbent assay (ELISA) were used to detect their effects on cell viability, and the protein expression of plasminogen activator inhibitor‐1 (PAI‐1), urokinase‐type plasminogen activator (uPA), uPA receptor (uPAR) and their secretion. The paired Student’s t ‐test was used for statistical analysis. Results TGF‐β1 significantly stimulated PAI‐1 and soluble uPAR (suPAR) secretion of SCAP cells ( P  < 0.05), whereas uPA secretion was inhibited. Accordingly, TGF‐β1 induced both PAI‐1 and uPAR protein expression of SCAP cells. SB431542 (an ALK5/Smad2/3 inhibitor) pretreatment and coincubation prevented the TGF‐β1‐induced PAI‐1 and uPAR of SCAP. U0126 attenuated the TGF‐β1‐induced expression/secretion of uPAR, but not PAI‐1 in SCAP. SB431542 reversed the TGF‐β1‐induced decline of uPA. Conclusions TGF‐β1 may affect the repair/regeneration activities of SCAP via differential increase or decrease of PAI‐1, uPA and uPAR. These effects induced by TGF‐β1 are associated with ALK5/Smad2/3 and MEK/ERK activation. Elucidation the signalling pathways and effects of TGF‐β1 is useful for treatment of immature teeth with open apex by revascularization/revitalization procedures and tissue repair/regeneration.

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