An investigation of crosstalk between Wnt/β-catenin and transforming growth factor-β signaling in androgenetic alopecia
Open Access
- 1 July 2016
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Medicine
- Vol. 95 (30), e4297
- https://doi.org/10.1097/md.0000000000004297
Abstract
Background: Wnt and transforming growth factor-β (TGF-β) signaling pathways are known to be involved in the pathogenesis of androgenetic alopecia (AGA). However, the way that Wnt and TGF-β 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-β 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-β signaling molecules in both balding and nonbalding hair follicles isolated from scalp specimens. Furthermore, we evaluated the activation of Wnt and TGF-β 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 TβRI and TβRII, and the protein expression of TGF-β1 was elevated in balding hair follicles. To investigate the crosstalk between Wnt and TGF-β signaling, we used SB431542 to inhibit the TGF-β 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 β-catenin was increased. On the other hand, we suppressed the Wnt signaling by XAV939 in nonbalding DP cells, which displayed that the level of β-catenin and LEF1 was significantly inhibited; however, the level of active TGF-β1 and the phosphorylation of Smad2 and Akt were up-regulated. Conclusions: These data indicate that crosstalk between Wnt/β-catenin and TGF-β signaling pathways may exist as one of the important mechanisms contributing to AGA.Keywords
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