The receptor for advanced glycation end-products (RAGE), a member of the immunoglobulin superfamily, is expressed in various cell types and mediates cellular responses to a wide range of ligands. The activation of RAGE triggers complex signaling pathways that drive inflammatory, oxidative, and proliferative responses, which are increasingly implicated in the pathogenesis of skin diseases. Despite its well-established roles in conditions such as diabetes, cancer, and chronic inflammation, the contribution of RAGE to skin pathologies remains underexplored. This review synthesizes current findings on RAGE’s involvement in the pathophysiology of skin diseases, including conditions such as psoriasis, atopic dermatitis, and lichen planus, focusing on its roles in inflammatory signaling, tissue remodeling, and skin cancer progression. Additionally, it examines RAGE-modulating treatments investigated in dermatological contexts, highlighting their potential as therapeutic options. Given RAGE’s significance in a variety of skin conditions, further research into its mediated pathways may uncover new opportunities for targeted interventions in skin-specific RAGE signaling.
Fibroblasts are among the most abundant cell types in the human body, playing crucial roles in numerous physiological processes, including the structural maintenance of the dermis, production of extracellular matrix components, and mediation of inflammatory responses. Despite their importance, fibroblasts remain one of the least characterized cell populations. The advent of single-cell analysis techniques, particularly single-cell RNA sequencing (scRNA-seq) and fluorescence-activated cell sorting (FACS), has enabled detailed investigations into fibroblast biology. In this study, we present an extensive analysis of fibroblast surface markers suitable for cell sorting and subsequent functional studies. We reviewed over three thousand research articles describing fibroblast populations and their markers, characterizing and comparing subtypes based on their surface markers, as well as their intra- and extracellular proteins. Our detailed analysis identified a variety of distinct fibroblast subpopulations, each with unique markers, characteristics dependent on their location, and the physiological or pathophysiological environment. These findings underscore the diversity of fibroblasts as a cellular population and could lead to the development of novel diagnostic and therapeutic tools.
Advancements in single-cell analyzis technologies, particularly single-cell RNA sequencing (scRNA-seq) and Fluorescence-Activated Cell Sorting (FACS), have enabled the analyzis of cellular diversity by providing resolutions that were not available previously. These methods enable the simultaneous analyzis of thousands of individual transcriptomes, facilitating the classification of cells into distinct subpopulations, based on transcriptomic differences, adding a new level of complexity to biomolecular and medical research. Fibroblasts, despite being one of the most abundant cell types in the human body and forming the structural backbone of tissues and organs, remained poorly characterized for a long time. This is largely due to the high morphological similarity between different types of fibroblasts and the lack of specific markers to identify distinct subpopulations. Once thought to be cells responsible solely for the synthesis of extracellular matrix (ECM) components, fibroblasts are now recognized as active participants in diverse physiological processes, including inflammation and antimicrobial responses. However, defining the molecular profile of fibroblast subpopulations remains a significant challenge. In this comprehensive review, which is based on over two thousand research articles, we focus on the identification and characterization of fibroblast subpopulations and their specific surface markers, with an emphasis on their potential as molecular targets for selective cell isolation. By analyzing surface markers, alongside intra- and extracellular protein profiles, we identified multiple fibroblast subtypes within the female reproductive system. These subtypes exhibit distinct molecular signatures and functional attributes, shaped by their anatomical localization and the surrounding physiological or pathological conditions. Our findings underscore the heterogeneity of fibroblasts and their diverse roles in various biological contexts. This improved understanding of fibroblast subpopulations paves the way for innovative diagnostic and therapeutic strategies, offering the potential for precision targeting of specific fibroblast subsets in clinical applications.
Purinergic P2X7 receptors are involved in cellular processes such as inflammation, proliferation, and tissue remodeling, although their significance in human skin physiology remains poorly understood. In this study, we demonstrated strong P2X7 receptor immunoreactivity in the basal and granular layers of the epidermis. Cutaneous expression of P2X7 receptors was further confirmed at the level of specific mRNA and protein in cultured primary human keratinocytes and dermal fibroblasts. To reveal a possible role of these receptors in regulation of keratinocyte and fibroblast function, the cells were treated with a P2X7 agonist BzATP, or its selective antagonist A438079. Cell proliferation and viability were assessed using an immunofluorescence-based cell counter, and cell migration was evaluated by wound healing assay. P2X7 stimulation with BzATP significantly inhibited keratinocyte proliferation and migration, while P2X7 inhibition with A438079 significantly enhanced keratinocyte migration. In contrast, fibroblasts displayed minimal response to either treatment. These findings indicate that P2X7 regulates keratinocyte growth, and purinergic signaling may play a role in the skin. Our data also suggest that selective P2X7 inhibition may support re-epithelialization under conditions associated with impaired wound healing.
Background/Objectives: Chronic endometritis (CE) is a subclinical inflammation of the endometrium that affects female fertility. Although awareness of its impact on reproductive outcomes has increased significantly, clinical management—especially the diagnostic value of hysteroscopy and the effectiveness of perioperative antibiotic prophylaxis in improving fertility—remains unclear. Methods: This retrospective analysis involved 136 infertile women (30–44 years) who underwent diagnostic hysteroscopy between 2022 and 2023 at the Military Institute of Medicine in Warsaw. Women with intrauterine pathologies or other infertility factors were excluded. Hysteroscopic indicators of chronic endometritis (CE) included micropolyps and endometrial hyperemia. Endometrial biopsies were stained with CD138 and CE was diagnosed based on ≥5 plasma cells per 10 high-power fields. A single oral dose of azithromycin was administered post-procedure and pregnancy outcomes were assessed 12 months later. Results: CE was histologically confirmed in 29.2% of patients. The presence of micropolyps demonstrated a strong correlation with CE (p < 0.0001), although CE was also found in 21% of patients with normal hysteroscopic findings. While CE status did not significantly influence pregnancy rates, patients who received azithromycin exhibited a significantly higher conception rate (53% vs. 21%, p = 0.022). Additionally, secondary infertility was associated with higher reproductive success compared to primary infertility (54% vs. 24%, p = 0.022). Conclusions: Micropolyps are a specific hysteroscopic marker of CE. However, histologic inflammation markers may be present even in the absence of abnormal hysteroscopic findings. Furthermore, the routine use of antibiotic prophylaxis is associated with improved reproductive outcomes.
Endometriosis is a complex disorder associated with dysregulated immune, hormonal, and microenvironmental signaling. Extracellular vesicles (EVs) are important mediators of intercellular communication and may contribute to disease pathogenesis, biomarker discovery, and therapeutic targeting. Here, we systematically reviewed the literature on EVs in endometriosis, focusing on EV classification, isolation and characterization methods, and the functional relevance of EV-associated cargo. A total of 50 original studies were included and evaluated in the context of current International Society for Extracellular Vesicles (ISEV) recommendations. Our analysis revealed marked heterogeneity in EV nomenclature, biological sources, and methodological approaches. Although most studies used standard EV markers, the assessment of sample purity and inclusion of negative controls was inconsistent. Further studies using standardized workflows and well-characterized cohorts are needed to clarify their biological and clinical significance.