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

Seunghee Lee; Jungyoon Ohn; Bo Mi Kang; Sungjoo Tommy Hwang; Ohsang Kwon

doi:10.1016/j.jare.2023.11.014

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

J Adv Res. 2023 Nov 14:S2090-1232(23)00351-X. doi: 10.1016/j.jare.2023.11.014. Online ahead of print.

Authors

Seunghee Lee¹, Jungyoon Ohn², Bo Mi Kang², Sungjoo Tommy Hwang³, Ohsang Kwon⁴

Affiliations

¹ Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, South Korea; Laboratory of Cutaneous Aging and Hair Research, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, South Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul 03080, South Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea.
² Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, South Korea; Laboratory of Cutaneous Aging and Hair Research, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, South Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul 03080, South Korea.
³ Dr. Hwang's Hair-Hair Clinic, Seoul 06035, South Korea.
⁴ Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, South Korea; Laboratory of Cutaneous Aging and Hair Research, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, South Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul 03080, South Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea. Electronic address: oskwon@snu.ac.kr.

PMID: 37972887
DOI: 10.1016/j.jare.2023.11.014

Abstract

Introduction: 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.

Objectives: To evaluate the effects of ALDH2 activation on oxidative stress in HFs and hair growth promotion.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Aldehyde dehydrogenase 2; Hair follicle; Hair growth; Outer root sheath; Oxidative stress; β-catenin.