First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2022 Jan 28;47(1):72-78. doi: 10.11817/j.issn.1672-7347.2022.210131.
The pathogenesis of androgenetic alopecia (AGA) 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 AGA. This study aims to investigate the role of AR up-regulation in the pathogenesis of AGA and underlying mechanisms.
A total of 46 male AGA patients (AGA 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 , , and were analyzed using real-time PCR. Human dermal papilla cells were transfected with siRNA to inhibit the expression of . MiR-1 and miR-1 inhibitors were transfected simultaneously or separately into cells and then the changes in AR protein expression were detected.
The levels of DHT and HSP27 in the AGA 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 0.05]. However, there was no significant difference in serum HSP27 and AR levels among AGA patients with different degrees of hair loss (>0.05). Correlation analysis showed that there was a positive correlation between HSP27 level and DHT level in the AGA patients (<0.05). The level of mRNA in scalp tissue was negatively correlated with that of mRNA (<0.05). Compared with the control group, the levels of HSP27 protein, AR protein, mRNA, and mRNA in scalp tissues of AGA group were significantly increased (0.05). The up-regulation of HSP27 in scalp tissues of AGA patients was closely related to the increased levels of AR. However, the level of miR-1 in scalp tissues of AGA patients was significantly down-regulated, contrary to the expression of AR (<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 <0.05).
HSP27 could combine with miR-1 to up-regulate AR levels, which is closely related to the development of AGA.
雄激素性脱发（AGA）的发病机制与雄激素及其代谢途径水平有关。雄激素与雄激素受体（AR）的结合取决于热休克蛋白 27（HSP27）的辅助。HSP27 与 microRNAs（miR）-1 结合可调节 AR 水平。然而，HSP27 和 miR-1 是否共同参与 AGA 的发病机制尚不清楚。本研究旨在探讨 AR 上调在 AGA 发病机制中的作用及其潜在机制。
共纳入 2019 年 9 月至 2020 年 2 月广州医科大学第一附属医院收治的 46 例 AGA 患者（AGA 组）和同期 52 例健康对照者。采用酶联免疫吸附法检测患者和健康对照者血清中二氢睾酮（DHT）和 HSP27 水平。采用 Western blot 检测患者和健康对照者头皮组织中 HSP27 和 AR 的蛋白表达。采用实时 PCR 分析 、 、和 的水平。用 siRNA 转染人真皮乳头细胞以抑制 的表达。同时或分别转染 miR-1 和 miR-1 抑制剂入细胞，然后检测 AR 蛋白表达的变化。
AGA 组的 DHT 和 HSP27 水平分别为（361.4±187.7）pg/mL 和（89.4±21.8）ng/mL，均高于对照组的（281.8±176.6）pg/mL 和（41.2±13.7）ng/mL（均<0.05）。然而，不同脱发程度的 AGA 患者血清 HSP27 和 AR 水平无显著差异（>0.05）。相关性分析显示，AGA 患者 HSP27 水平与 DHT 水平呈正相关（<0.05）。AGA 患者头皮组织中 mRNA 水平与 mRNA 水平呈负相关（<0.05）。与对照组相比，AGA 组头皮组织中 HSP27 蛋白、AR 蛋白、 mRNA 和 mRNA 水平均显著升高（<0.05）。AGA 患者头皮组织中 HSP27 的上调与 AR 水平的升高密切相关。然而，AGA 患者头皮组织中 miR-1 的水平显著下调，与 AR 的表达相反（<0.05）。进一步的细胞研究表明，抑制人真皮乳头细胞中 HSP27 或 miR-1 的表达可抑制 AR 的表达，同时抑制 HSP27 和 miR-1 的表达对 AR 具有累积效应，差异均有统计学意义（均<0.05）。
HSP27 可与 miR-1 结合上调 AR 水平，这与 AGA 的发生发展密切相关。
