Activation of mitochondrial aldehyde dehydrogenase 2 promotes hair growth in human hair follicles.

[Display omitted] • Aldehyde dehydrogenase 2 (ALDH2) levels in human hair follicles (HFs) are significantly increased during the anagen phase. • ALDH2 expression is primarily localized in the outer root sheath of human HFs. • Activation of ALDH2 in HFs leads to anagen induction and subsequent hair shaft elongation. • ALDH2 activation triggers reactive oxygen species scavenging in HFs and upregulates β-catenin signaling. • Modulation of ALDH2 may be a promising therapeutic approach for inducing the anagen phase, providing novel insights into the impact of ALDH2 activation on HFs. Hair loss is a common phenomenon associated with various environmental and genetic factors. Mitochondrial dysfunction-induced oxidative stress has been recognized as a crucial determinant of hair follicle (HF) biology. Aldehyde dehydrogenase 2 (ALDH2) mitigates oxidative stress by detoxifying acetaldehyde. This study investigated the potential role of ALDH2 modulation in HF function and hair growth promotion. To evaluate the effects of ALDH2 activation on oxidative stress in HFs and hair growth promotion. The modulatory role of ALDH2 on HFs was investigated using an ALDH2 activator. ALDH2 expression in human HFs was evaluated through in vitro immunofluorescence staining. Ex vivo HF organ culture was employed to assess hair shaft elongation, while the fluorescence probe 2′,7′- dichlorodihydrofluorescein diacetate was utilized to detect reactive oxygen species (ROS). An in vivo mouse model was used to determine whether ALDH2 activation induces anagen. During the anagen phase, ALDH2 showed significantly higher intensity than that in the telogen phase, and its expression was primarily localized along the outer layer of HFs. ALDH2 activation promoted anagen phase induction by reducing ROS levels and enhancing reactive aldehyde clearance, which indicated that ALDH2 functions as a ROS scavenger within HFs. Moreover, ALDH2 activation upregulated Akt/GSK 3β/β-catenin signaling in HFs. Our findings highlight the hair growth promotion effects of ALDH2 activation in HFs and its potential as a promising therapeutic approach for promoting anagen induction. [ABSTRACT FROM AUTHOR]