An investigation of crosstalk between Wnt/beta-catenin and transforming growth factor-beta signaling in androgenetic alopecia

作者：Lu, Gui-Qing; Wu, Zhi-Bo; Chu, Xiao-Yan; Bi, Zhi-Gang; Fan, Wei-Xin^*

来源：Medicine, 2016, 95(30): e4297.

DOI：10.1097/MD.0000000000004297

• androgenetic alopecia
• dermal papilla cell
• hair follicle
• SB431542
• TGF-beta
• Wnt
• XAV939

Background: Wnt and transforming growth factor-beta (TGF-beta) signaling pathways are known to be involved in the pathogenesis of androgenetic alopecia (AGA). However, the way that Wnt and TGF-beta 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-beta 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-beta signaling molecules in both balding and nonbalding hair follicles isolated from scalp specimens. Furthermore, we evaluated the activation of Wnt and TGF-beta 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 T beta RI and T beta RII, and the protein expression of TGF-beta 1 was elevated in balding hair follicles. To investigate the crosstalk between Wnt and TGF-beta signaling, we used SB431542 to inhibit the TGF-beta 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 beta-catenin was increased. On the other hand, we suppressed the Wnt signaling by XAV939 in nonbalding DP cells, which displayed that the level of beta-catenin and LEF1 was significantly inhibited; however, the level of active TGF-beta 1 and the phosphorylation of Smad2 and Akt were up-regulated.
Conclusions: These data indicate that crosstalk between Wnt/beta-catenin and TGF-beta signaling pathways may exist as one of the important mechanisms contributing to AGA.

• 出版日期2016-7
• 单位南京医科大学