Commensal microbiome promotes hair follicle regeneration by inducing keratinocyte HIF-1α signaling and glutamine metabolism

Wang, Gaofeng; Sweren, Evan; Andrews, William; Li, Yue; Chen, Junjun; Xue, Yingchao; Wier, Eric M.; Alphonse, Martin P.; Luo, Li; Miao, Yong; Chen, Ruosi; Zeng, Dongqiang; Lee, Sam; Li, Ang; Dare, Erika; Kim, Dongwon; Archer, Nathan K.; Reddy, Sashank K.; Resar, Linda M.S.; Hu, Zhiqi; Grice, Elizabeth A.; Kane, Maureen A.; Garza, Luis A.

doi:10.1126/sciadv.abo7555

Cited by 15 publications

(10 citation statements)

References 60 publications

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“…For example, VEGFA (vascularization endothelial growth factor A) has been shown to regulate vascularization and vessel size around the hair follicle, thus altering the size of follicles as blood vessels are required to provide nutrients. 13 In addition, Gaofeng Wang et al 16 found that activation of HIF1A signaling by inducing tissue hypoxia promoted wound-induced hair follicle neogenesis. Quercetin, luteolin, and kaempferol were identified as the major active compounds in SEZW.…”

Section: Discussionmentioning

confidence: 99%

Promotion of Hair Regrowth in Androgenetic Alopecia with Supplemented Erzhi Wan: Exploring Its Mechanism Using Network Pharmacology and Molecular Docking

Ji,

Ma,

Feng

et al. 2023

CCID

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Supplemented Erzhi Wan (SEZW) is a Traditional Chinese Medicine commonly used in the treatment of androgenetic alopecia (AGA). This study aims to verify the effectiveness of SEZW for the treatment of AGA in mice and explore the potential molecular mechanisms underlying its function using network pharmacology and molecular docking. Methods: Forty mice were divided into five groups: Control, AGA-model, AGA-Positive, SEZW Low Dose, and SEZW High Dose. Hair regrowth in mice was evaluated by scoring hair on days 0, 14, and 28 post-treatment and weighing mouse hair on day 28 posttreatment. The targets of the active compounds of SEZW were obtained using the Traditional Chinese Medicine Database. AGArelated targets were downloaded from five databases. Then, the overlapping genes were identified. A protein-protein interaction network was constructed using the STRING database. Hub targets were determined through analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Finally, molecular docking of active compounds and hub targets was performed. Results: Hair regrowth in mice in the SEZW treatment groups was significantly enhanced relative to that in the AGA-model mice. A total of 59 potential drug-disease targets were identified. Based on the GO/KEGG analysis results, oxidative stress and gland development were identified as potential mechanisms of action of SEZW in AGA treatment. The PI3K-Akt and AGE-RAGE signaling pathways and seven hub targets were identified as the potential underlying mechanism of SEZW function. Molecular docking results showed that the most active SEZW compounds bind stably to several of the candidate disease targets. Conclusion: SEZW is effective in the treatment of AGA in a mouse model. Combined with network pharmacological analysis, the potential mechanisms, signaling pathways, and hub targets of SEZW in the treatment of AGA were identified, providing new ideas for further studies.

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Section: Discussionmentioning

confidence: 99%

Promotion of Hair Regrowth in Androgenetic Alopecia with Supplemented Erzhi Wan: Exploring Its Mechanism Using Network Pharmacology and Molecular Docking

Ji,

Ma,

Feng

et al. 2023

CCID

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“…Non-healing chronic wounds also exhibit overrepresentation of facultative anaerobes, such as Enterobacter and Proteus , compared to wounds that heal within six months [ 232 ]. Moreover, the recent observations that specific strains of S. aureus are associated with poor healing outcomes [ 82 ] and infection [ 83 ], whereas others bolster host response and skin regeneration [ 233 , 234 ], highlight the need for subspecies-level profiling to elucidate the microbial drivers of poor healing in the elderly.…”

Section: Wound Pathology Ageing and Infectionmentioning

confidence: 99%

The Skin Microbiome: Current Landscape and Future Opportunities

Smythe

Wilkinson

2023

IJMS

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Our skin is the largest organ of the body, serving as an important barrier against the harsh extrinsic environment. Alongside preventing desiccation, chemical damage and hypothermia, this barrier protects the body from invading pathogens through a sophisticated innate immune response and co-adapted consortium of commensal microorganisms, collectively termed the microbiota. These microorganisms inhabit distinct biogeographical regions dictated by skin physiology. Thus, it follows that perturbations to normal skin homeostasis, as occurs with ageing, diabetes and skin disease, can cause microbial dysbiosis and increase infection risk. In this review, we discuss emerging concepts in skin microbiome research, highlighting pertinent links between skin ageing, the microbiome and cutaneous repair. Moreover, we address gaps in current knowledge and highlight key areas requiring further exploration. Future advances in this field could revolutionise the way we treat microbial dysbiosis associated with skin ageing and other pathologies.

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“…The hypoxia-inducible factor 1-alpha (HIF-1α) signal plays an important role in the regulation of energy metabolism. Recently, Wang et al reported that hypoxia microenvironment-active HIF-1α signaling increases glutamine metabolism in keratinocytes and promotes HF regeneration [64].…”

Section: Metabolic Reprogramming In the Hair Follicle Cyclementioning

confidence: 99%

Overview of the Circadian Clock in the Hair Follicle Cycle

et al. 2023

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The circadian clock adapts to the light–dark cycle and autonomously generates physiological and metabolic rhythmicity. Its activity depends on the central suprachiasmatic pacemaker. However, it also has an independent function in peripheral tissues such as the liver, adipose tissue, and skin, which integrate environmental signals and energy homeostasis. Hair follicles (HFs) maintain homeostasis through the HF cycle, which depends heavily on HF stem cell self-renewal and the related metabolic reprogramming. Studies have shown that circadian clock dysregulation in HFs perturbs cell cycle progression. Moreover, there is increasing evidence that the circadian clock exerts a significant influence on glucose metabolism, feeding/fasting, stem cell differentiation, and senescence. This suggests that circadian metabolic crosstalk plays an essential role in regulating HF regeneration. An improved understanding of the role of the circadian clock in HFs may facilitate the discovery of new drug targets for hair loss. Therefore, the present review provides a discussion of the relationship between the circadian clock and HF regeneration, mainly from the perspective of HF metabolism, and summarizes the current understanding of the mechanisms by which HFs function.

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Commensal microbiome promotes hair follicle regeneration by inducing keratinocyte HIF-1α signaling and glutamine metabolism

Cited by 15 publications

References 60 publications

Promotion of Hair Regrowth in Androgenetic Alopecia with Supplemented Erzhi Wan: Exploring Its Mechanism Using Network Pharmacology and Molecular Docking

Promotion of Hair Regrowth in Androgenetic Alopecia with Supplemented Erzhi Wan: Exploring Its Mechanism Using Network Pharmacology and Molecular Docking

The Skin Microbiome: Current Landscape and Future Opportunities

Overview of the Circadian Clock in the Hair Follicle Cycle

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