Epidermal ET-1 signal induces activation of resting hair follicles by upregulating the PI3K/AKT pathway in the dermis
(2024) In FASEB Journal 38(4).- Abstract
The prevalence of alopecia has increased recently. Hair loss is often accompanied by the resting phase of hair follicles (HFs). Dermal papilla (DP) plays a crucial role in HF development, growth, and regeneration. Activating DP can revive resting HFs. Augmenting WNT/β-catenin signaling stimulates HF growth. However, the factors responsible for activating resting HFs effectively are unclear. In this study, we investigated epidermal cytokines that can activate resting HFs effectively. We overexpressed β-catenin in both in vivo and in vitro models to observe its effects on resting HFs. Then, we screened potential epidermal cytokines from GEO DATASETs and assessed their functions using mice models and skin-derived precursors (SKPs).... (More)
The prevalence of alopecia has increased recently. Hair loss is often accompanied by the resting phase of hair follicles (HFs). Dermal papilla (DP) plays a crucial role in HF development, growth, and regeneration. Activating DP can revive resting HFs. Augmenting WNT/β-catenin signaling stimulates HF growth. However, the factors responsible for activating resting HFs effectively are unclear. In this study, we investigated epidermal cytokines that can activate resting HFs effectively. We overexpressed β-catenin in both in vivo and in vitro models to observe its effects on resting HFs. Then, we screened potential epidermal cytokines from GEO DATASETs and assessed their functions using mice models and skin-derived precursors (SKPs). Finally, we explored the molecular mechanism underlying the action of the identified cytokine. The results showed that activation of WNT/β-catenin in the epidermis prompted telogen–anagen transition. Keratinocytes infected with Ctnnb1-overexpressing lentivirus enhanced SKP expansion. Subsequently, we identified endothelin 1 (ET-1) expressed higher in hair-growing epidermis and induced the proliferation of DP cells and activates telogen-phase HFs in vivo. Moreover, ET-1 promotes the proliferation and stemness of SKPs. Western blot analysis and in vivo experiments revealed that ET-1 induces the transition from telogen-to-anagen phase by upregulating the PI3K/AKT pathway. These findings highlight the potential of ET-1 as a promising cytokine for HF activation and the treatment of hair loss.
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- author
- Gao, Ying ; Fan, Zhimeng LU ; Xiao, Xing ; Kong, Deqiang ; Han, Jimin and Chu, Weiwei
- organization
- publishing date
- 2024-02-29
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- endothelin 1, epidermis, hair follicle, hair loss, skin-derived precursors
- in
- FASEB Journal
- volume
- 38
- issue
- 4
- article number
- e23476
- publisher
- Wiley
- external identifiers
-
- pmid:38334392
- scopus:85184726841
- ISSN
- 0892-6638
- DOI
- 10.1096/fj.202302207R
- language
- English
- LU publication?
- yes
- id
- 18e66ff2-5a1d-45c6-9d45-c8a57674770d
- date added to LUP
- 2024-02-22 14:01:11
- date last changed
- 2024-04-22 00:00:16
@article{18e66ff2-5a1d-45c6-9d45-c8a57674770d,
abstract = {{<p>The prevalence of alopecia has increased recently. Hair loss is often accompanied by the resting phase of hair follicles (HFs). Dermal papilla (DP) plays a crucial role in HF development, growth, and regeneration. Activating DP can revive resting HFs. Augmenting WNT/β-catenin signaling stimulates HF growth. However, the factors responsible for activating resting HFs effectively are unclear. In this study, we investigated epidermal cytokines that can activate resting HFs effectively. We overexpressed β-catenin in both in vivo and in vitro models to observe its effects on resting HFs. Then, we screened potential epidermal cytokines from GEO DATASETs and assessed their functions using mice models and skin-derived precursors (SKPs). Finally, we explored the molecular mechanism underlying the action of the identified cytokine. The results showed that activation of WNT/β-catenin in the epidermis prompted telogen–anagen transition. Keratinocytes infected with Ctnnb1-overexpressing lentivirus enhanced SKP expansion. Subsequently, we identified endothelin 1 (ET-1) expressed higher in hair-growing epidermis and induced the proliferation of DP cells and activates telogen-phase HFs in vivo. Moreover, ET-1 promotes the proliferation and stemness of SKPs. Western blot analysis and in vivo experiments revealed that ET-1 induces the transition from telogen-to-anagen phase by upregulating the PI3K/AKT pathway. These findings highlight the potential of ET-1 as a promising cytokine for HF activation and the treatment of hair loss.</p>}},
author = {{Gao, Ying and Fan, Zhimeng and Xiao, Xing and Kong, Deqiang and Han, Jimin and Chu, Weiwei}},
issn = {{0892-6638}},
keywords = {{endothelin 1; epidermis; hair follicle; hair loss; skin-derived precursors}},
language = {{eng}},
month = {{02}},
number = {{4}},
publisher = {{Wiley}},
series = {{FASEB Journal}},
title = {{Epidermal ET-1 signal induces activation of resting hair follicles by upregulating the PI3K/AKT pathway in the dermis}},
url = {{http://dx.doi.org/10.1096/fj.202302207R}},
doi = {{10.1096/fj.202302207R}},
volume = {{38}},
year = {{2024}},
}