p75 neurotrophin receptor regulates NGF-induced myofibroblast differentiation and collagen synthesis through MRTF-A.
Exp Cell Res
; 383(1): 111504, 2019 10 01.
Article
em En
| MEDLINE
| ID: mdl-31325438
ABSTRACT
Myofibroblasts are characterized by de novo expression of α-smooth muscle actin (α-SMA) and play a key role in tissue repair and remodeling. In addition to TGF-ß1, recent studies have shown that nerve growth factor (NGF) has effects on myofibroblast differentiation and collagen synthesis. However, the regulatory mechanism remains poorly defined. NGF effects are mediated by the specific expression of the NGF neurotrophic tropomyosin-receptor kinase A (TrkA) and p75 neurotrophin receptor (p75NTR). Using NIH/3T3 fibroblast cell lines, we examined the induction of myofibroblast differentiation stimulated by NGF. Our findings showed that p75NTR was in keeping with the expression of α-SMA. Herein, we investigated the role of p75NTR in NGF-induced myofibroblast differentiation and collagen synthesis in these cells using lentivirus transfection to overexpress and knock down. Our results showed that p75NTR was preferentially expressed and was sufficient to induce actin cytoskeleton remodeling, which was required for NGF-induced α-SMA expression. Furthermore, NGF induced nuclear translocation of MRTF-A, an effect that was regulated by p75NTR, and required for α-SMA and collagen-I expression in myofibroblasts. Using a novel MRTF-A pathway inhibitor, CCG-203971, we further demonstrated the requirement of MRTF-A nuclear localization and activity in NGF-induced α-SMA expression. In conclusion, we conclude that p75NTR regulates NGF-induced myofibroblast differentiation and collagen synthesis through MRTF-A. Regulation of NGF-p75NTR interactions represents a promising therapy for fibrotic disorders.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
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Transativadores
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Colágeno
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Receptores de Fator de Crescimento Neural
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Receptor trkA
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Fator de Crescimento Neural
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Miofibroblastos
Limite:
Animals
Idioma:
En
Revista:
Exp Cell Res
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China