Androgenetic alopecia (AGA) is the most common form of non-scarring hair loss, driven by genetic factors and increased sensitivity of scalp hair follicles to dihydrotestosterone (DHT), which causes progressive miniaturization of dermal papilla cells and shortens the hair growth phase. The precise molecular pathogenesis of AGA remains incompletely understood. The study aimed to elucidate the regulatory mechanism between secreted frizzled-related protein 2 (SFRP2) and follistatin-like 1 (FSTL1), explore their impact on DHT-induced mitochondrial dysfunction and senescence in dermal papilla cells (DPCs), elucidate the effect of the SFRP2-FSTL1 axis on oxidative stress-related DPCs changes, and identify new therapeutic targets for AGA treatment. In the study, SFRP2 was highly expressed in the DPCs of AGA patients. Knocking down SFRP2 improved hair regeneration and follicle morphology within AGA model mice, promoting proliferation, migration, and invasion of DPCs in vitro. SFRP2 knockdown also alleviated inflammation, senescence, mitochondrial dysfunction, and oxidative stress. SFRP2 was found to bind to FSTL1, thereby promoting FSTL1 protein stability. Knocking down FSTL1 counteracted the negative effects of SFRP2 overexpression in vitro. In conclusion, SFRP2 emerges as a critical regulator in AGA by promoting stability and activity of FSTL1, establishing a novel SFRP2-FSTL1 axis that exacerbates DHT-driven pathogenic changes in DPCs. These findings identify SFRP2 and FSTL1 as key mediators of androgen-induced cellular dysfunction and suggest that disrupting this axis could offer a promising therapeutic strategy for slowing or reversing the progression of AGA.

Rosacea is a chronic inflammatory skin condition primarily affecting the face, characterized by symptoms such as persistent redness, visible blood vessels, papules, and pustules. Current treatments, including topical agents and systemic antibiotics, are often limited by poor skin penetration, local irritation, or the risk of systemic adverse effects and antibiotic resistance. This study designed, fabricated, and evaluated a novel ROS-responsive hydrogel microneedle (MN) system for the co-delivery of tofacitinib (a JAK inhibitor) and azelaic acid (A ZA) to treat rosacea. The hypothesis was that this Tofa/AZA@HPA-MN platform would enable triggered drug release in the high-ROS environment of inflamed skin, enhancing therapeutic efficacy and safety compared to conventional topical delivery. Topical tofacitinib and AZA were found to ameliorate LL37-induced murine rosacea-like inflammation, partly via JAK/STAT inhibition. A ROS-responsive hydrogel (HPA) was synthesized and fabricated into robust MNs, demonstrating effective skin penetration and retention. In vitro, these MNs displayed accelerated drug release under oxidative conditions and protected keratinocytes from H 2 O 2 -induced stress. In vivo, the Tofa/AZA@HPA-MNs proved superior to conventional topical Tofa + AZA and empty MNs, significantly reducing inflammation, tissue ROS levels, and JAK/STAT activation in a rosacea model. Crucially, safety assessments revealed no significant systemic toxicity, addressing the major translational concern regarding the systemic risks of JAK inhibitors. The developed system offers a promising, safe, and more effective targeted therapeutic strategy for rosacea by enabling triggered drug release directly within the inflamed skin.

Background: Skin and subcutaneous diseases generate large chronic morbidity, yet their burden is seldom interpreted alongside population ageing, pandemic-era disruption, and forward service planning. We quantified burden, ecological correlates, pandemic-period deviation, and exploratory forecasts. Methods: We combined GBD 2023 extracts, authenticated Results Tool annual series, and World Bank ageing metrics. Global burden was summarised for 1990 and 2023. Country-level ecological analyses used 2023 mortality rates from 198 countries and territories and GBD risk exposure indicators. We also assembled a supplementary Asia-Pacific comparison using authenticated 2023 Results Tool exports for 39 locations defined operationally as World Bank East Asia & Pacific plus South Asia. Pandemic-period deviation compared observed 2020-2023 age-standardized rates with log-linear counterfactuals fitted to 2010-2019 trends. Exploratory projections to 2050 used damped-trend exponential smoothing. Findings: Between 1990 and 2023, the global share of people aged 65 years and older rose from 6.07% to 9.98%, while the age-standardized incidence rate increased from 49457.7 to 52095.8 per 100,000 and the age-standardized mortality rate increased from 1.29 to 1.85 per 100,000. Deaths rose from 48,081 to 161,053. Higher population ageing remained negatively associated with mortality, but household air pollution (rho=0.269) and albuminuria prevalence (rho=0.356) were positively associated, and top-20 high-mortality settings had higher adult BMI exposure than other countries (median 17.99 vs 16.81). Relative to the pre-pandemic counterfactual, global mortality was 3.37% higher in 2023, whereas prevalence and incidence remained slightly below expected (-0.15% and -0.42%). Exploratory projections suggested further increases by 2050, reaching a death rate of 2.14 and a DALY rate of 500.5 per 100,000. In a supplementary Asia-Pacific comparison covering 39 locations, the unweighted mean mortality rate was 4.53 per 100,000 versus 1.85 globally, while the mean prevalence and incidence rates were 15555.0 and 50340.6 per 100,000, both slightly below global levels; the highest Asia-Pacific mortality was observed in Micronesia (Federated States of) (21.56), Marshall Islands (14.30), and Kiribati (13.98). Interpretation: Global skin burden rose alongside population ageing, but high standardized mortality clustered more strongly with ecological markers of structural vulnerability and metabolic risk than with ageing alone. Asia-Pacific comparisons showed that this excess fatal burden was concentrated particularly in Pacific island settings and selected South and Southeast Asian countries, even when non-fatal rates were closer to the global profile. Pandemic-period mortality drift and continued increases projected to 2050 reinforce the need to integrate skin care, chronic wound prevention, and infection control into healthy-ageing policy.

Androgenetic alopecia (AGA) is the most common hair disorder, but lacks effective treatments. This study explored the effects and mechanisms of Bletilla striata polysaccharide (BSP) on AGA and provided new directions for developing drugs for treating AGA. In the study, BSP improved the hair growth cycle and hair follicle morphology within AGA model mice, enhanced hair score, increased hair length, and elevated the number of hair follicles. BSP also reduced inflammation and oxidative stress, lowered dihydrotestosterone (DHT) content, regulated androgen receptor (AR) activity, inhibited the production of inflammatory factors and malondialdehyde (MDA) accumulation, and increased superoxide dismutase (SOD) activity and glutathione (GSH) levels. In vitro, BSP restored the proliferation and migration of DHT-induced dermal papilla cells (DPCs), inhibited their inhibition, alleviated cell senescence, and enhanced the antioxidant activity of H2O2-induced DPCs. Network pharmacology analysis suggested that BSP may influence AGA progression by modulating the nuclear factor kappa B (NF-κB) signaling pathway and oxidative stress through prostaglandin-endoperoxide synthase 2 (PTGS2), and BSP inhibits PTGS2 expression. Furthermore, PTGS2 overexpression antagonized the effects of BSP. In conclusion, BSP inhibits PTGS2, thereby suppressing the activation of prostaglandin E2 (PGE2) and NF-κB signaling, which improves oxidative stress and cell senescence, ultimately alleviating the progression of AGA and promoting hair growth. This finding provides a potential drug intervention target and a new strategy for the treatment of AGA.

[This corrects the article DOI: 10.1016/j.mtbio.2022.100534.].

BACKGROUND:Ultraviolet B (UVB) irradiation can damage melanocytes, leading to skin disorders such as photoaging, melanoma, and vitiligo. While UVB-induced apoptosis and autophagy are well-studied, the role of ferroptosis, an iron-dependent form of programmed cell death, in melanocyte damage remains unclear. METHODS:Human epidermal melanocytes were exposed to UVB irradiation, and the effects on cell viability, apoptosis, reactive oxygen species (ROS) production, and iron metabolism were assessed using MTT, flow cytometry, DHE staining, and iron assays. RNA sequencing and bioinformatics analyses were conducted to explore differential gene expression and pathway activation. Ferrostatin-1 (Fer-1) was used to inhibit ferroptosis and evaluate its protective effects. RESULTS:UVB exposure significantly reduced melanocyte viability, increased apoptosis, elevated ROS levels, and disrupted iron metabolism. Fer-1 treatment alleviated these effects by inhibiting ferroptosis. RNA sequencing showed activation of Ras, Rap1, PI3K-Akt, and Mitogen-Activated Protein Kinase (MAPK) signaling pathways, along with alterations in iron metabolism-related genes (e.g., FAXDC2, CYP3A5). Although classic ferroptosis core genes were not notably changed, the MAPK pathway and iron metabolism may indirectly contribute to UVB-induced ferroptosis. CONCLUSION:UVB-induced melanocyte damage involves ferroptosis, potentially triggered by the MAPK pathway and iron metabolism. Fer-1 effectively protects melanocytes by inhibiting ferroptosis, underscoring its therapeutic potential for UVB-related skin disorders.

BACKGROUND:In recent decades, our understanding of the pathogenesis and pathophysiology of skin photoaging has improved considerably, thereby enhancing preventive and management strategies. The bibliometric analysis demonstrates the chronological trends of publications, highlighting the most influential studies related to skin photoaging. OBJECTIVE:This study aims to identify and analyze the top 100 most-cited articles related to skin photoaging to offer bibliometric information. METHODS:The Web of Science database was searched to obtain publications on skin photoaging. Information from the top 100 most-cited articles was extracted and analyzed using Microsoft Excel 2019 and VOSviewer (version 1.6.18). RESULTS:The top 100 most-cited articles on skin photoaging received a total of 23 925 citations and an average of 239 citations per article. The top most-cited article received 1019 citations and 30.88 citations per article. The publication year ranged from 1995 to 2010, with a peak period of top publications between 2001 and 2005. The Journal of Investigative Dermatology and the Journal of the American Academy of Dermatology published the largest number of top-cited articles. The articles originated from nine different countries, with The United States as the highest contributor. Fisher GJ was the most productive first author from the University of Michigan in the United States and published a total of three articles. A total of 62 keywords were included and grouped into three clusters: 'matrix metalloproteinase', 'collagen' and 'radiation'. The article types include only reviews and original articles. Prevention and treatment-related studies were the most common research focus, followed by pathogenesis, pathophysiology, clinical features and screening methods. CONCLUSION:This bibliometric analysis on skin photoaging demonstrated a major upward trend in the prevention and treatment of skin photoaging, which provides a foundation for future research.

Cutaneous photoaging, induced by chronic exposure to ultraviolet (UV) radiation, typically manifests as alterations in both the physical appearance and functional properties of the skin and may predispose individuals to cancer development. Recent studies have demonstrated the reparative potential of exosomes derived from mesenchymal stem cells in addressing skin damage, while specific reports highlight their efficacy in ameliorating skin photoaging. However, the precise role of exosomes derived from human hair follicle mesenchymal stem cells (HFMSC-Exos) in the context of cutaneous photoaging remains largely unexplored. We successfully isolated HFMSC-Exos using the ultracentrifugation technique. In cellular experiments, we assessed the migration of human dermal fibroblasts (HDFs) through scratch and transwell assays, evaluated the angiogenesis of human umbilical vein endothelial cells through angiogenesis assays, and examined the expression levels of collagen and matrix metalloproteinase 1 (MMP-1) using Western blotting and quantitative reverse transcription polymerase chain reaction. Furthermore, we established a nude mouse model of photoaging to observe wrinkle formation on the dorsal surface of the animals, as well as to assess dermal thickness and collagen fiber generation through histological staining. Ultimately, we performed RNA sequencing on skin tissues from mice before and after treatment to elucidate the relevant underlying mechanisms. Our findings revealed that HFMSC-Exos effectively enhanced the migration and proliferation of HDFs and upregulated the expressions of transforming growth factor-beta 1 (TGF-beta 1), p-Smad2/p-Smad3, collagen type 1, and collagen type 3 while concurrently down-regulating MMP-1 levels in HDFs. Additionally, mice in the HFMSC-Exo group showed quicker wrinkle healing and increased collagen production. HFMSC-Exos miR-125b-5p was demonstrated to reduce skin photoaging by increasing profibrotic levels via TGF-beta 1 expression. UV-irradiated HDFs and photoaged nude mouse skin showed low TGF-beta 1 expressions, whereas overexpression of TGF-beta 1 in HDFs increased collagen type 1, collagen type 3, and p-Smad2/p-Smad3 expressions while decreasing MMP-1 expression. HDFs overexpressing TGF-beta 1 produced more collagen and altered the Smad pathway. This study demonstrated, both in vitro and in vivo, that HFMSC-Exos increased collagen formation, promoted HDF cell proliferation and migration, and reversed the senescence of UV-irradiated HDFs. TGF-beta 1 was identified as a target of HFMSC-Exos miR-125b-5p, which controls photoaging via regulating the Smad pathway. The antiphotoaging capabilities of HFMSC-Exos may occur via the miR-125b-5p/TGF-beta 1/Smad axis, suggesting a promising therapeutic approach for treating skin photoaging.

BACKGROUND:Exosomes, as nanosized extracellular vesicles, play a crucial role in regulating cellular communication and mediating biological processes related to skin aging, including oxidative stress, inflammation, and extracellular matrix homeostasis. This study aims to provide a comprehensive overview of the current status, key trends, and hotspots in exosome research focused on skin aging. METHODS:Bibliometric analysis was performed using CiteSpace (Version 6.4.R1), VOSviewer (Version 1.6.20), and Excel (v2021). Data were collected from the Science Citation Index Expanded of Web of Science Core Collection, covering publications from 2015 to 2024. Analyses included publication trends, country/region distribution, institutional contributions, key journals, influential authors, citation patterns, exosome sources, and research hotspots. RESULTS:A total of 165 relevant publications (114 original articles and 51 reviews) were identified, with a significant upward trend in publications since 2020, peaking in 2024. China contributed the largest number of publications (84), followed by South Korea (28) and the USA (20). Shanghai Jiao Tong University (China) was the most productive institution, while International Journal of Molecular Sciences published the highest number of articles in this field. BEHFAR A, GAO W, and PARK JH were the most productive authors, and Shabbir A's 2015 article in Stem Cells and Development had the highest local citation score (532). Human-derived exosomes (80 %) were the primary focus, with adipose (29 %) and skin (26 %) as the main tissue sources. Key research hotspots included "exosomes," "mesenchymal stem cells," "skin aging," "collagen," and emerging themes such as "miRNAs" and "drug delivery." CONCLUSION:Research on exosomes in skin aging has grown rapidly, with China, South Korea, and the USA leading in output and influence. The field is transitioning from basic mechanistic studies to translational applications, with a focus on exosome-mediated regeneration, anti-aging therapies, and drug delivery systems. Future directions should emphasize international collaboration, quality improvement, and exploration of novel exosome sources and mechanisms.

Rosacea, an inflammatory skin disorder with complex pathogenesis, remains poorly understood. Through integrative bioinformatics and experimental approaches, we identified 304 differentially expressed genes in erythrotelangiectasia rosacea (ETR), primarily enriched in lipid metabolism pathways. Support vector machine (SVM), linear regression analyses and network analysis revealed ACADVL and ACSL5 as potential therapeutic targets. Immunological profiling demonstrated distinctive immune cell infiltration, with elevated M0 and M1 macrophages in patients with ETR. Immunofluorescence validation confirmed significant ACSL5 upregulation and increased M1 macrophage infiltration in the rosacea mouse model. The co-localization of ACSL5 with M1 macrophage markers suggests a mechanistic link between lipid metabolism and inflammatory responses. These findings provide new insights into ETR pathogenesis and highlight ACSL5 as a promising therapeutic target for inflammatory skin disorders.

Abstract Sarcoidosis, a multisystemic granulomatous disease with unknown etiology, is characterized by formation of noncaseating granulomas, which can affect all organs. Recent studies have made outstanding achievement in understanding the pathology, etiology, genetics, and immune dysregulation involved in granuloma formation of sarcoidosis. Antigen stimulation in genetically predisposed individuals enhances the phagocytic activity of antigen-presenting cells, including macrophages and dendritic cells. CD4 + T cells initiate dysregulated immune responses and secrete significant quantities of inflammatory cytokines, including interleukin (IL)-2 and interferon-gamma (IFN-γ), which play a crucial role in modulating the aggregation and fusion of macrophages to form granulomas. The current therapeutic strategies focus on blocking the formation and spread of granulomas to protect organ function and alleviate symptoms. The efficacy of traditional treatments, such as glucocorticoids and immunosuppressants, has been confirmed in the management of sarcoidosis. Promising therapeutic agents encompass inhibitors of cytokines, like those targeting tumor necrosis factor (TNF)-α, as well as inhibitors of signaling pathways, such as Janus kinase (JAK) inhibitors, which exhibit favorable prospects for application. Although there has been progress in the identification of biomarkers for the diagnosis, prognosis, activity and severity of sarcoidosis, specific and sensitive biomarkers have yet to be identified. This review outlines recent advancements in the molecular mechanisms and therapeutic strategies for the sarcoidosis.

Background: Prior studies have suggested a significant connection between fasting insulin (FI) and androgenetic alopecia (AGA), but the exact cause of this connection and underlying molecular mechanism has not been clarified. In this study, a Mendelian randomization (MR) analysis was utilized to discover the causal associations between FI and AGA. Methods: Genome-wide association study (GWAS) data for FI and AGA were retrieved, and bidirectional MR analysis was conducted. FI-associated genes were identified through expression quantitative trait loci (eQTL) analysis, with enrichment analysis and a protein-protein interaction (PPI) network used to explore potential pathways and core genes. Results: Forward MR analysis revealed a significant causal relationship between elevated FI levels and AGA (P=0.027, OR=43.944). Reverse MR analysis found no causal effect of AGA on FI (P=0.808, OR=1.0001). A total of 92 FI-associated genes were analyzed, with enrichment results indicating involvement in glycine, serine, and threonine metabolic pathways. EIF2B4 and NRBP1 were identified as potential core genes linking FI and AGA. Conclusion: By using MR analysis, this study verified the possible causative connection between FIns and AGA by MR analysis. The core genes EIF2B4 and NRBP1, along with biological processes such as glycosylation and amino acid metabolism, may serve as crucial links.

Background: Skin photoaging, a degenerative skin process driven primarily by chronic ultraviolet radiation exposure, has become a key focus in dermatological research and clinical practice, with growing demand for effective preventive and therapeutic strategies. Despite the expansion of research in this field, no systematic bibliometric analysis has characterized the global research landscape of photoaging therapy over the past decade, leaving a gap in understanding its developmental trajectory. Methods: We retrieved publications related to photoaging therapy from the Web of Science (WoS) Core Collection, with data searches and exports completed on August 26, 2025. The search covered literature published between January 1, 2015, and December 31, 2024, using the strategy: TS= (“skin photoaging” OR “photoaging” OR “photoaging of skin” OR “solar aging of skin”) AND TS= (therapy OR therapies OR treatment). After screening for publication timeframe (2015–2024), document types (articles and reviews), and language (English), 1172 eligible articles were included. Data analysis was performed using CiteSpace (Version 6.4.R1), VOSviewer (Version 1.6.20), Tableau (2025.2) and Excel (v2021) to examine annual publication trends, global distribution of research output, productivity and influence of countries, institutions, journals, and authors, collaborative networks, reference co-citations, and keyword co-occurrences. Results: Over the 2015–2024 period, research on photoaging therapy showed a steady upward trend in annual publications, increasing from 60 in 2015 to 199 in 2024 (a more than threefold growth). A total of 75 countries/regions, 1831 institutions, and 5860 authors contributed to the field. China led in publication volume (336 papers, 28.67%), followed by the United States (232 papers, 19.8%) and South Korea (231 papers, 19.71%), though China’s citation-per-publication rate (14.92) was relatively low. Among institutions, Kyung Hee University (South Korea) was the most productive (40 papers, 822 citations), while China Medical University (China) had the highest citation-per-publication ratio (29.32) among top institutions. The Journal of Cosmetic Dermatology published the most relevant papers (70), and the International Journal of Molecular Sciences had the highest total citations (1390, IF=4.9). Hwang, Eunson (21 papers) was the most productive author, with top authors predominantly affiliated with Kyung Hee University. Keyword co-occurrence analysis identified four core clusters: ultraviolet radiation-induced damage and mechanisms, photoaging-related skin diseases, prevention/treatment strategies, and pigmentation regulation/local therapies. Emerging research trends included the use of exosomes, microRNA, NF-κB signaling modulation, and platelet-rich plasma for regenerative repair. Conclusion: This comprehensive bibliometric analysis quantifies the global research landscape and trends in photoaging therapy from 2015 to 2024, highlighting the field’s rapid expansion, key contributing entities, and core research themes. It identifies emerging directions (e.g., exosome-based interventions, inflammatory signaling regulation) and gaps (e.g., limited regional collaboration among top institutions, need for improved citation impact of Chinese publications). This study provides valuable insights for guiding future research, facilitating international collaboration, and accelerating the translation of basic science to clinical practice in photoaging therapy.

[This corrects the article DOI: 10.3389/fmicb.2020.570269.].

[This corrects the article DOI: 10.3389/fphar.2021.752148.].

Photoaging is characterized by chronic inflammation in response to ultraviolet (UV) radiation. UV radiation causes skin cells to produce reactive oxygen species (ROS), which causes oxidative stress and inflammation. ROS can reversibly or irreversibly destroy different cellular compounds, including nucleic acids, proteins, free amino acids, lipids, lipoproteins, carbohydrates, and connective tissue macromolecules. Ferroptosis is a kind of programmed cell death caused by iron dependence and lipid peroxidation and has been recently discovered. Its occurrence is primarily related to iron metabolism, antioxidants, lipid peroxidation, and other processes. In addition, high levels of ROS can trigger oxidative stress, altering the redox balance within cells and thus initiating ferroptosis. Ferroptosis has been implicated in UV-driven skin photoaging. Moreover, UV radiation from sunlight can regulate numerous ferroptosis-linked genes. This review will focus on the function of ferroptosis in UV radiation-damaged skin cells. We hope to draw attention to the significance of ferroptosis regulation in the prevention and treatment of skin photoaging.

Background:Vitiligo is a complex acquired pigmentary disorder whose pathogenesis is closely linked to oxidative stress. Although bilirubin, a potent endogenous antioxidant, has been implicated in various dermatological conditions, its specific role in vitiligo remains poorly defined. This study aims to investigate the causal associations between bilirubin and vitiligo using Mendelian randomization (MR) analysis, complemented by bioinformatics validation to unravel the underlying molecular mechanisms. Methods:Genome-wide association study (GWAS) data pertaining to vitiligo and bilirubin were obtained, followed by the execution of a bidirectional MR analysis. Additionally, we performed a bioinformatics analysis using microarray datasets to identify differentially expressed genes (DEGs) in relation to bilirubin in patients with vitiligo. Pathway enrichment and gene interaction networks were constructed to explore the molecular mechanisms linking bilirubin to vitiligo pathogenesis. Results:Forward MR analysis demonstrated a significant causal relationship between elevated levels of total bilirubin (P=0.038) and direct bilirubin (P=0.013) with reduced risk of vitiligo. In contrast, reverse MR analysis showed no significant causal effect of vitiligo on bilirubin (P>0.05). Bioinformatics analyses identified 136 DEGs in generalized vitiligo, 32 in segmental vitiligo, and 9 in non-segmental vitiligo. Enrichment analysis highlighted significant associations with oxidative stress-related pathways, including PI3K-Akt and JAK-STAT signaling, which are critical in melanocyte survival and immune regulation. Conclusion:This study provides robust evidence supporting a causal relationship between elevated bilirubin and a reduced risk of vitiligo, driven by its antioxidant properties. The identified DEGs and enriched pathways further elucidate the molecular mechanisms of bilirubin in the pathogenesis of vitiligo through oxidative stress, and may provide insights for future therapeutic strategies.

cryptococcus neoformans (C. neoformans) is a crucial opportunistic fungus that possesses an encapsulated fungal pathogen. The cryptococcal capsule is mainly composed of the polysaccharide glucuronoxylomannan (GXM). Macrophages form the first-line innate defense against cryptococcosis; however, the underlying mechanism remains unclear. In this study, GXM-treated RAW264.7 macrophages showed a notably reduced survival rate and increased apoptosis, accompanied by the promoted inducible nitric oxide synthase (iNOS) expression and NO production. Signal transducer and activator of transcription 1 (STAT1) expression was also found to be directly proportional to GXM concentration; STAT1 knockdown could alleviate GXM-induced proliferation decrease and apoptosis increase of macrophages, as well as reduce M1 polarization, iNOS expression and NO release. In conclusion, this study concluded that GXM was the main virulence factor of C. neoformans, which is critical in determining the mechanism of GXM-mediated protective immune response postinfection. The STAT1 signal pathway mediates the effect of GXM stimulation on macrophages, potentially providing a reference for further understanding the biological role of GXM.

Background:Androgenetic alopecia (AGA) is a common pattern hair loss in which perifollicular fibrosis drives hair follicle miniaturization. Inflammatory-fibrotic cross talk centered on TGF-β/Smad, with input from Wnt/β-catenin and Notch, disrupts epithelial-mesenchymal communication and impairs regeneration. Summary:We summarize evidence linking chronic inflammation to fibroblast/myofibroblast activation and excessive extracellular matrix deposition around hair follicles, highlight dermoscopic features that may reflect fibrotic burden, and outline a continuum between AGA and fibrosing patterned alopecias. We review anti-fibrotic strategies directed at TGF-β, Wnt/β-catenin, and Notch signaling, and how combining antiandrogenic, anti-inflammatory, and anti-fibrotic approaches could address both hormonal and structural drivers. Key Messages:Perifollicular fibrosis is integral to AGA progression and may underlie incomplete treatment responses. Dermoscopic signs such as perifollicular hyperpigmentation and whitish perifollicular structures may correlate with histologic fibrosis and merit validation. Pathway-directed anti-fibrotic agents targeting TGF-β and Wnt/Notch show anti-fibrotic activity in other organs but require AGA-specific testing.