RIPK4 suppresses the TGF-ß1 signaling pathway in HaCaT cells.
Cell Biol Int
; 44(3): 848-860, 2020 Mar.
Article
em En
| MEDLINE
| ID: mdl-31825120
ABSTRACT
Receptor-interacting serine/threonine kinase 4 (RIPK4) and transforming growth factor-ß 1 (TGF-ß1) play critical roles in the development and maintenance of the epidermis. A negative correlation between the expression patterns of RIPK4 and TGF-ß signaling during epidermal homeostasis-related events and suppression of RIPK4 expression by TGF-ß1 in keratinocyte cell lines suggest the presence of a negative regulatory loop between the two factors. So far, RIPK4 has been shown to regulate nuclear factor-κB (NF-κB), protein kinase C (PKC), wingless-type MMTV integration site family (Wnt), and (mitogen-activated protein kinase) MAPK signaling pathways. In this study, we examined the effect of RIPK4 on the canonical Smad-mediated TGF-ß1 signaling pathway by using the immortalized human keratinocyte HaCaT cell line. According to our results, RIPK4 inhibits intracellular Smad-mediated TGF-ß1 signaling events through suppression of TGF-ß1-induced Smad2/3 phosphorylation, which is reflected in the upcoming intracellular events including Smad2/3-Smad4 interaction, nuclear localization, and TGF-ß1-induced gene expression. Moreover, the kinase activity of RIPK4 is required for this process. The in vitro wound-scratch assay demonstrated that RIPK4 suppressed TGF-ß1-mediated wound healing through blocking TGF-ß1-induced cell migration. In conclusion, our results showed the antagonistic effect of RIPK4 on TGF-ß1 signaling in keratinocytes for the first time and have the potential to contribute to the understanding and treatment of skin diseases associated with aberrant TGF-ß1 signaling.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Queratinócitos
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Proteínas Serina-Treonina Quinases
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Proteína Smad2
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Proteína Smad3
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Proteína Smad4
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Fator de Crescimento Transformador beta1
Limite:
Humans
Idioma:
En
Revista:
Cell Biol Int
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Turquia