Regulation of the regenerative activity of dental pulp stem cells from exfoliated deciduous teeth (SHED) of children by TGF-ß1 is associated with ALK5/Smad2, TAK1, p38 and MEK/ERK signaling.
Aging (Albany NY)
; 12(21): 21253-21272, 2020 11 04.
Article
em En
| MEDLINE
| ID: mdl-33148869
ABSTRACT
Transforming growth factor-ß1 (TGF-ß1) regulates wound healing/regeneration and aging processes. Dental pulp stem cells from human exfoliated deciduous teeth (SHED) are cell sources for treatment of age-related disorders. We studied the effect of TGF-ß1 on SHED and related signaling. SHED were treated with TGF-ß1 with/without pretreatment/co-incubation by SB431542, U0126, 5Z-7-oxozeaenol or SB203580. Sircol collagen assay, 3-(4,5-Dimethylthiazol-2-yl)-2,5- diphenyl tetrazolium bromide (MTT) assay, alkaline phosphatase (ALP) assay, RT-PCR, western blotting and PathScan phospho-ELISA were used to measure the effects. We found that SHED expressed ALK1, ALK3, ALK5, TGF-RII, betaglycan and endoglin mRNA. TGF-ß1 stimulated p-Smad2, p-TAK1, p-ERK, p-p38 and cyclooxygenase-2 (COX-2) protein expression. It enhanced proliferation and collagen content of SHED that were attenuated by SB431542, 5Z-7-oxozeaenol and SB203580, but not U0126. TGF-ß1 (0.5-1 ng/ml) stimulated ALP of SHED, whereas 5-10 ng/ml TGF-ß1 suppressed ALP. SB431542 reversed the effects of TGF-ß1. However, 5Z-7-oxozeaenol, SB203580 and U0126 only reversed the stimulatory effect of TGF-ß1 on ALP. Four inhibitors attenuated TGF-ß1-induced COX-2 expression. TGF-ß1-stimulated TIMP-1 and N-cadherin was inhibited by SB431542 and 5Z-7-oxozeaenol. These results indicate that TGF-ß1 affects SHED by differential regulation of ALK5/Smad2/3, TAK1, p38 and MEK/ERK. TGF-ß1 and SHED could potentially be used for tissue engineering/regeneration and treatment of age-related diseases.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Regeneração
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Células-Tronco
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Dente Decíduo
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MAP Quinase Quinase Quinases
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Quinases de Proteína Quinase Ativadas por Mitógeno
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Polpa Dentária
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MAP Quinases Reguladas por Sinal Extracelular
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Proteínas Quinases p38 Ativadas por Mitógeno
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Proteína Smad2
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Fator de Crescimento Transformador beta1
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article