Association of fibrosis in the bulge portion with hair follicle miniaturization in androgenetic alopecia

Li, Kaitao; Liu, Fang; Sun, Yang; Gan, Yuyang; Zhu, De-Cong; Wang, Hailin; Wang, Jin; Chen, Ruosi; Fan, Zhexiang; Liu, Bingcheng; Fu, Danlan; Miao, Yong

doi:10.1016/j.jaad.2021.01.078

Cited by 6 publications

(4 citation statements)

References 4 publications

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“…[16,17] Mast cell play an important role in fibrotic, [18] and research have proved fibrosis occurs in the bulge region of AGAaffected HFs and correlates with their miniaturization stage. [19] In our study, γδ T cell, central memory CD8 + cell and mast cell were significantly more infiltrated in the bald group than in the haired group. This imbalance in immune cell infiltration may correlate with suppression of hair growth and miniaturization of hair follicle due to excessive DHT binds to the androgen receptors.…”

Section: Discussionsupporting

confidence: 46%

“…[ 30 ] Further research could validate the effectivity of MMP9 inhibitors in mouse model of AGA, and MMP9 inhibitor would provide an additional option for male AGA treatment. There is a positive correlation between the fibrosis of the bulge portion and the miniaturization of AGA-affected hair follicles, [ 19 ] but there is no anti-fibrotic therapy in current treatments, indicating drugs inhibiting fibrosis are potential therapy to reverse hair miniaturization during AGA development. Though AGA is currently regarded as non-immunological hair loss, the immune cells infiltrate is significant difference between bald and hair scalp of male AGA, whether the immune cells are associated with HFIP remain unclear.…”

Section: Discussionmentioning

confidence: 99%

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Identification of immune microenvironment changes, immune-related pathways and genes in male androgenetic alopecia

Xiong,

Tang,

Chen

et al. 2023

Medicine

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Background: Although androgenetic alopecia (AGA) is classified as a non-inflammatory alopecia, histological evidence of microinflammation has long been recognized. However, changes in the immune microenvironment, immune-related pathways and the expression of immune-related genes (IRGs) involved in AGA remain unclear. Methods: The microarray gene expression data (GSE36169) from patients with male AGA were analyzed. gene set enrichment analysis (GSEA) among statistically changed genes was done. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses among differentially expressed genes were performed. differentially expressed genes were screened to identify IRGs based on the ImmPort database. The cytohubba-MCC plugin of Cytoscape was applied to screen hub immune genes. The infiltration levels of 28 immune cells were quantified adopting single-sample GSEA (ssGSEA) algorithm. The microarray gene expression data (GSE90594) of male AGA was analyzed to validate hub IRGs genes and differential infiltrated immune cells. Results: The ssGSEA revealed γδT cell, central memory CD8+ T cell, mast cell, immature B cell, activated CD8+ T cell, effector memory CD4+ T cell, eosinophil and neutrophil were significantly increased infiltration in the bald scalp. GSEA showed statistically changed genes were most enriched in immune related pathways, including innate immune system, adaptive immune system, cytokine signaling, interferon-γ signaling, interferon signaling and interleukins signaling. The 4 hub IRGs, including matrix metallopeptidase 9, protein tyrosine phosphatase receptor type C, bone morphogenetic protein 2, and thrombospondin 1, were enriched in the pathways of allograft rejection, coagulation and interferon-γ response. Conclusion: In summary, we proposed that the increase in γδ T cells, central memory CD8+ T cells, activated CD8+ T cell as well as the infiltration of mast cells contributed to immune microenvironment changes in male AGA. The 4 hub IRGs may be involved in the development and progression of hair loss in male AGA through interferon-γ signal pathways.

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Section: Discussionsupporting

confidence: 46%

Section: Discussionmentioning

confidence: 99%

Identification of immune microenvironment changes, immune-related pathways and genes in male androgenetic alopecia

Xiong,

Tang,

Chen

et al. 2023

Medicine

View full text Add to dashboard Cite

show abstract

“…On the other hand, mast cell decrease dramatically during anagen, while γδT cell numbers remain unchanged during the hair cycle [16,17]. Mast cell play an important role in brotic [18], and research have proved brosis occurs in the bulge region of AGA-affected HFs and correlates with their miniaturization stage [19]. In our study, γδ T cell, central memory CD8 + cell and mast cell were signi cantly more in ltrated in the bald group than in the haired group.…”

Section: Discussionmentioning

confidence: 99%

Identification of Immune Microenvironment Changes, Immune-Related Pathways and Genes in Male Androgenetic Alopecia

Xiong

Tang

Hai-ju

et al. 2023

Preprint

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Although Androgenetic Alopecia (AGA) is classified as a non-inflammatory alopecia, histological evidence of microinflammation has long been recognized. However, the changes in the immune microenvironment, the immune-related pathway and the expression of Immune-related genes (IRGs) involved in AGA remain unclear. The microarray gene expression data (GSE36169) from patients with male AGA were analyzed. Gene Set Enrichment Analysis (GSEA) among statistically changed genes was done. KEGG and GO analyses among differentially expressed genes (DEGs) were performed. DEGs were screened to identify IRGs based on the ImmPort database. The cytohubba-MCC plugin of Cytoscape was applied to screen hub immune genes. The infiltration levels of 28 immune cells were quantified adopting single-sample GSEA (ssGSEA) algorithm. The microarray gene expression data (GSE90594) of male AGA was analyzed to validate hub IRGs genes and differential infiltrated immune cells. The ssGSEA revealed γδT cell, central memory CD8+ T cell, mast cell, immature B cell, activated CD8+ T cell, effector memory CD4+ T cell, eosinophil and neutrophil were significantly increased infiltration in the bald scalp. GSEA showed statistically changed genes were most enriched in immune related pathways, including innate immune system, adaptive immune system, cytokine signaling, interferon-γ signaling, interferon signaling and interleukins signaling. The four hub IRGs, including MMP9, PTPRC, BMP2 and THBS1, were enriched in the pathways of allograft rejection, coagulation and interferon-γ response. In summary, we proposed that the increase in γδ T cells, central memory CD8+ T cells, activated CD8+ T cell as well as the infiltration of mast cells contributed to immune microenvironment changes in male AGA. The 4 hub IRGs may be involved in the development and progression of hair loss in male AGA through interferon-γ signal pathways.

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“…It affects over 50% of men by the age of 50 and typically manifests in the temples, vertex, and mid-frontal scalp region 1 . AGA is characterized by a shortened anagen phase, prolonged telogen phase, and miniaturization of hair follicles 2 , 3 . The pathogenesis of AGA is primarily driven by dihydrotestosterone (DHT), which is converted from testosterone via the 5-α reductase enzyme 4 .…”

Section: Introductionmentioning

confidence: 99%

The AR/miR-221/IGF-1 pathway mediates the pathogenesis of androgenetic alopecia

Li,

Sun,

Liu

et al. 2023

Int. J. Biol. Sci.

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Androgenetic alopecia (AGA) affects more than half of the adult population worldwide and is primarily caused by the binding of dihydrotestosterone (DHT) to androgen receptors (AR). However, the mechanisms by which AR affects hair follicles remain unclear. In our study, we found that miR-221 significantly suppressed hair growth and the proliferation of dermal papilla cells (DPCs) and dermal sheath cells (DSCs) in AGA patients. Interestingly, miR-221 and AR were mainly co-located in the same part of the hair follicle. Mechanistic analysis revealed that AR directly promoted the transcription of miR-221, which in turn suppressed IGF-1 expression, leading to the inactivation of the MAPK pathway in DPCs and the PI3K/AKT pathway in DSCs. In AGA patients, miR-221 expression was positively correlated with AR expression and negatively correlated with IGF-1 expression. Our findings indicate that miR-221, as a direct target of AR, plays a crucial role in the pathogenesis of AGA, making it a novel biomarker and potential therapeutic target for treating AGA.

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Association of fibrosis in the bulge portion with hair follicle miniaturization in androgenetic alopecia

Cited by 6 publications

References 4 publications

Identification of immune microenvironment changes, immune-related pathways and genes in male androgenetic alopecia

Identification of immune microenvironment changes, immune-related pathways and genes in male androgenetic alopecia

Identification of Immune Microenvironment Changes, Immune-Related Pathways and Genes in Male Androgenetic Alopecia

The AR/miR-221/IGF-1 pathway mediates the pathogenesis of androgenetic alopecia

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