Therapeutic potential of isoproterenol in androgenetic alopecia: activation of hair follicle stem cells via the PI3K/AKT/β-Catenin signaling pathway
Abstract Background Androgenetic alopecia (AGA) is characterized by the depletion or dormancy of hair follicle stem cells (HFSCs), leading to hair thinning and miniaturization. Reactivating the dormant HFSCs is a promising therapeutic approach. Adrenergic β2 receptor (ADRB2) activation has been show...
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BMC
2025-06-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-025-04418-y |
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| author | Jiarui Zhang Jinxing Peng Zhexiang Fan Hailin wang Lihong Wen Yong Miao Yu Chai Zhiqi Hu Ruosi Chen |
| author_facet | Jiarui Zhang Jinxing Peng Zhexiang Fan Hailin wang Lihong Wen Yong Miao Yu Chai Zhiqi Hu Ruosi Chen |
| author_sort | Jiarui Zhang |
| collection | DOAJ |
| description | Abstract Background Androgenetic alopecia (AGA) is characterized by the depletion or dormancy of hair follicle stem cells (HFSCs), leading to hair thinning and miniaturization. Reactivating the dormant HFSCs is a promising therapeutic approach. Adrenergic β2 receptor (ADRB2) activation has been shown to promote hair growth in animal models via the Sonic Hedgehog (SHH) pathway, but its potential for treating clinical AGA patients remains unexamined. Methods We investigated the role of the PI3K/AKT signaling pathway in AGA pathogenesis, focusing on the hair follicle-sympathetic nerve axis. The ADRB2 agonist, isoproterenol (ISO), was administered to assess its effects on AGA hair follicle organ culture model and HFSC proliferation. The mechanisms underlying these effects were explored by analyzing the PI3K/AKT/β-Catenin pathway. Results Our results showed abnormal PI3K/AKT pathway expression in AGA hair follicles, with associated defects in the hair follicle-sympathetic nerve axis. ISO treatment accelerated AGA hair follicle growth and promoted the proliferation of HFSC. Mechanistically, ISO facilitated the HFSC activation by modulating the PI3K/AKT/β-Catenin pathway. Conclusions ISO effectively promotes hair growth in both animal models and AGA patients. ISO stimulating the proliferation of dormant cell population enriched in HFSC. This process was likely mediated by the PI3K/AKT/β-Catenin pathway. These findings provide novel insights into the reactivation of HFSCs and suggest that adrenergic signaling stimulation may be a promising strategy for managing hair loss. |
| format | Article |
| id | doaj-art-617dde1c6fbb4b589f5fe9d7cd1849c6 |
| institution | OA Journals |
| issn | 1757-6512 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj-art-617dde1c6fbb4b589f5fe9d7cd1849c62025-08-20T02:10:31ZengBMCStem Cell Research & Therapy1757-65122025-06-0116111510.1186/s13287-025-04418-yTherapeutic potential of isoproterenol in androgenetic alopecia: activation of hair follicle stem cells via the PI3K/AKT/β-Catenin signaling pathwayJiarui Zhang0Jinxing Peng1Zhexiang Fan2Hailin wang3Lihong Wen4Yong Miao5Yu Chai6Zhiqi Hu7Ruosi Chen8Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of Cardiac Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Guangdong Cardiovascular Institute, Southern Medical UniversityDepartment of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of Plastic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityDepartment of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of Traumatic Orthopedics Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical UniversityDepartment of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical UniversityAbstract Background Androgenetic alopecia (AGA) is characterized by the depletion or dormancy of hair follicle stem cells (HFSCs), leading to hair thinning and miniaturization. Reactivating the dormant HFSCs is a promising therapeutic approach. Adrenergic β2 receptor (ADRB2) activation has been shown to promote hair growth in animal models via the Sonic Hedgehog (SHH) pathway, but its potential for treating clinical AGA patients remains unexamined. Methods We investigated the role of the PI3K/AKT signaling pathway in AGA pathogenesis, focusing on the hair follicle-sympathetic nerve axis. The ADRB2 agonist, isoproterenol (ISO), was administered to assess its effects on AGA hair follicle organ culture model and HFSC proliferation. The mechanisms underlying these effects were explored by analyzing the PI3K/AKT/β-Catenin pathway. Results Our results showed abnormal PI3K/AKT pathway expression in AGA hair follicles, with associated defects in the hair follicle-sympathetic nerve axis. ISO treatment accelerated AGA hair follicle growth and promoted the proliferation of HFSC. Mechanistically, ISO facilitated the HFSC activation by modulating the PI3K/AKT/β-Catenin pathway. Conclusions ISO effectively promotes hair growth in both animal models and AGA patients. ISO stimulating the proliferation of dormant cell population enriched in HFSC. This process was likely mediated by the PI3K/AKT/β-Catenin pathway. These findings provide novel insights into the reactivation of HFSCs and suggest that adrenergic signaling stimulation may be a promising strategy for managing hair loss.https://doi.org/10.1186/s13287-025-04418-yIsoproterenolHair follicle stem cellPI3K/AKT/β-catenin signalingAndrogenetic alopeciaClinical trialHair regrowth |
| spellingShingle | Jiarui Zhang Jinxing Peng Zhexiang Fan Hailin wang Lihong Wen Yong Miao Yu Chai Zhiqi Hu Ruosi Chen Therapeutic potential of isoproterenol in androgenetic alopecia: activation of hair follicle stem cells via the PI3K/AKT/β-Catenin signaling pathway Stem Cell Research & Therapy Isoproterenol Hair follicle stem cell PI3K/AKT/β-catenin signaling Androgenetic alopecia Clinical trial Hair regrowth |
| title | Therapeutic potential of isoproterenol in androgenetic alopecia: activation of hair follicle stem cells via the PI3K/AKT/β-Catenin signaling pathway |
| title_full | Therapeutic potential of isoproterenol in androgenetic alopecia: activation of hair follicle stem cells via the PI3K/AKT/β-Catenin signaling pathway |
| title_fullStr | Therapeutic potential of isoproterenol in androgenetic alopecia: activation of hair follicle stem cells via the PI3K/AKT/β-Catenin signaling pathway |
| title_full_unstemmed | Therapeutic potential of isoproterenol in androgenetic alopecia: activation of hair follicle stem cells via the PI3K/AKT/β-Catenin signaling pathway |
| title_short | Therapeutic potential of isoproterenol in androgenetic alopecia: activation of hair follicle stem cells via the PI3K/AKT/β-Catenin signaling pathway |
| title_sort | therapeutic potential of isoproterenol in androgenetic alopecia activation of hair follicle stem cells via the pi3k akt β catenin signaling pathway |
| topic | Isoproterenol Hair follicle stem cell PI3K/AKT/β-catenin signaling Androgenetic alopecia Clinical trial Hair regrowth |
| url | https://doi.org/10.1186/s13287-025-04418-y |
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