An investigation of crosstalk between Wnt/ß-catenin and transforming growth factor-ß signaling in androgenetic alopecia.
Medicine (Baltimore)
; 95(30): e4297, 2016 Jul.
Article
em En
| MEDLINE
| ID: mdl-27472703
ABSTRACT
BACKGROUND:
Wnt and transforming growth factor-ß (TGF-ß) signaling pathways are known to be involved in the pathogenesis of androgenetic alopecia (AGA). However, the way that Wnt and TGF-ß signaling is altered in patients with AGA and whether there exists a crosstalk between them in pathogenetic process of AGA remain unclear.OBJECTIVES:
To investigate the expression of Wnt and TGF-ß signaling and the crosstalk between these 2 signaling pathways in AGA.METHODS:
Fifteen male patients with AGA were recruited for our research. Fifteen scalp specimens of the balding were collected from frontal areas, and 9 nonbalding were collected from occipital areas. We analyzed the expression and activation of downstream Wnt and TGF-ß signaling molecules in both balding and nonbalding hair follicles isolated from scalp specimens. Furthermore, we evaluated the activation of Wnt and TGF-ß signaling after either of them was blocked with the inhibitor in balding and nonbalding dermal papilla (DP) cells.RESULTS:
Compared with the nonbalding counterparts, the mRNA level of Wnt10a and LEF1 was decreased. But TßRI and TßRII, and the protein expression of TGF-ß1 was elevated in balding hair follicles. To investigate the crosstalk between Wnt and TGF-ß signaling, we used SB431542 to inhibit the TGF-ß signaling in balding DP cells and found that SB431542 significantly attenuated the phosphorylation of Smad2 and Akt. However, the mRNA level of Wnt10a, LEF1, and the nuclear translocation of ß-catenin was increased. On the other hand, we suppressed the Wnt signaling by XAV939 in nonbalding DP cells, which displayed that the level of ß-catenin and LEF1 was significantly inhibited; however, the level of active TGF-ß1 and the phosphorylation of Smad2 and Akt were up-regulated.CONCLUSIONS:
These data indicate that crosstalk between Wnt/ß-catenin and TGF-ß signaling pathways may exist as one of the important mechanisms contributing to AGA.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fator de Crescimento Transformador beta
/
Alopecia
/
Via de Sinalização Wnt
Tipo de estudo:
Observational_studies
Limite:
Adult
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Medicine (Baltimore)
Ano de publicação:
2016
Tipo de documento:
Article