Up - regulation of androgen receptor by heat shock protein 27 and miR - 1 induces pathogenesis of androgenic alopecia


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In humans

The pathogenesis of androgenetic alopecia (Androgenetic Alopecia) is related to the level of androgen and its metabolic pathways. The binding of androgen and androgen receptor (AR) depends on the assistance of heat shock protein 27 (HSP27). HSP27 combined with microRNAs (miR)-1 can regulate AR levels. However, it is not clear whether HSP27 and miR-1 jointly participate in the pathogenesis of Androgenetic Alopecia. This study aims to investigate the role of AR up-regulation in the pathogenesis of Androgenetic Alopecia and underlying mechanisms.
Methods: A total of 46 male Androgenetic Alopecia patients (Androgenetic Alopecia group), who admitted to the First Affiliated Hospital of Guangzhou Medical University from September 2019 to February 2020, and 52 healthy controls admitted to the same period were enrolled in this study. Serum levels of dihydrotestosterone (DHT) and HSP27 in patients and healthy controls were measured by ELISA. Western blotting was used to detect the protein expression of HSP27 and AR in scalp tissues of patients and the healthy controls. The levels of HSP27, AR, and miR-1 were analyzed using real-time PCR. Human dermal papilla cells were transfected with HSP27 siRNA to inhibit the expression of HSP27. MiR-1 and miR-1 inhibitors were transfected simultaneously or separately into cells and then the changes in AR protein expression were detected.
Results: The levels of DHT and HSP27 in the Androgenetic Alopecia group were (361.4±187.7) pg/mL and (89.4±21.8) ng/mL, respectively, which were higher than those in the control group [(281.8±176.6) pg/mL and (41.2±13.7) ng/mL, both P<0.05]. However, there was no significant difference in serum HSP27 and AR levels among Androgenetic Alopecia patients with different degrees of hair loss (P>0.05). Correlation analysis showed that there was a positive correlation between HSP27 level and DHT level in the Androgenetic Alopecia patients (P<0.05). The level of HSP27 mRNA in scalp tissue was negatively correlated with that of miR-1 mRNA (P<0.05). Compared with the control group, the levels of HSP27 protein, AR protein, HSP27 mRNA, and AR mRNA in scalp tissues of Androgenetic Alopecia group were significantly increased (P<0.05). The up-regulation of HSP27 in scalp tissues of Androgenetic Alopecia patients was closely related to the increased levels of AR. However, the level of miR-1 in scalp tissues of Androgenetic Alopecia patients was significantly down-regulated, contrary to the expression of AR (P<0.05). Further in cell studies showed that inhibition of HSP27 or miR-1 expression in human dermal papilla cells could inhibit the expression of AR, and inhibition of both HSP27 and miR-1 expression was found to have an accumulative effect on AR, with statistically significant differences (all P<0.05).
Conclusions: HSP27 could combine with miR-1 to up-regulate AR levels, which is closely related to the development of Androgenetic Alopecia.
Keywords: androgen alopecia; androgen receptor; heat shock protein 27; miR-1.