Browsing by Subject "Keloid"

Now showing 1 - 3 of 3
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    Functional histopathology of keloid disease
    (F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2015) Jumper, N.; Paus, R.; Bayat, A.
    Keloid disease is a benign, yet locally aggressive and recurrent cutaneous fibroproliferative condition characterised by excessive scarring. Unique to humans, keloids represent the end-point of a spectrum of abnormal wound healing, are aesthetically disfiguring and can cause major functional impairment. Its heterogeneous phenotype can confound clinical diagnosis leading to mismanagement. This review examines the histological morphology of keloid disease relative to the underlying pathobiology, places it in the context of other cutaneous fibroses and highlights gaps within the literature that hinder differential diagnosis. The pathological similarity to hypertrophic scarring, dermatofibrosarcoma protuberans, dermatofibroma and scleroderma emphasise the importance of detailing the architectural and cellular components of this unique entity. In the papillary dermis keloid tumours show a tongue-like advancing edge that resembles invasive tumour growth. A thickened but flattened epidermis, hyalinised haphazardly arranged collagen bundles that dominate the dermis with subsequent obliteration of the papillary-reticular boundary along with displacement and eventually destruction of skin appendages, exemplify additional hallmark findings associated with keloid disease. Compared to healthy skin, keloid scars show an increased type I/III collagen ratio, decreased fibrillin-1 and decorin expression, increased dermal cellularity and increased expression of fibronectin, versican, elastin and tenascin in the reticular dermis and hyaluronan and osteopontin in the epidermis. We illustrate these “pathognomonic” features of keloid disease by representative micrographs and discuss them in the context of inflammation, hypoxia and tension - as key elements of keloid disease. Finally, we highlight deficits within the keloid research literature as well as discuss important areas for future research in keloid histology.
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    LINC00937 suppresses keloid fibroblast proliferation and extracellular matrix deposition by targeting the miR-28-5p/MC1R axis
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Wan, Jing; He, Xiao-Lei; Jian, Qi-Chao; Fan, Zhi-Feng; Shi, Ying; Luo, Long-Fei
    Long noncoding RNAs (lncRNAs) are the most recently discovered class of noncoding RNAs. LncRNAs play a crucial role in multiple disorders. However, the role and mechanism of action of lncRNAs in keloids remain unclear. Here, qRT-PCR and western blotting assays were performed to determine the expression of genes and proteins, respectively. MTT assays were carried out to measure the proliferation of keloid fibroblasts. In addition, a luciferase activity assay was conducted to investigate the relationships between LINC00937 and miR-28-5p and between miR-28-5p and MC1R. The results showed that LINC00937 and MC1R were decreased, whereas miR-28-5p was increased in keloid tissues. LINC00937 overexpression in keloid fibroblasts could repress the extracellular matrix (ECM) deposition and cell proliferation and promote MC1R expression. Moreover, high expression of miR-28-5p and low expression of LINC00937 were detected in keloid fibroblasts. We further showed that LINC00937 promoted MC1R expression by sponging miR-28-5p. Finally, our data indicated that LINC00937 inhibited the ECM deposition and proliferation of keloid fibroblasts by inhibiting miR-28-5p and facilitating MC1R expression. Overall, LINC00937 suppressed the ECM deposition and proliferation of keloid fibroblasts by acting as an miR-28-5p sponge and promoting MC1R expression. Our data suggested that LINC00937 is a potential target for keloid treatment.
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    Upregulation of autophagy and glycolysis markers in keloid hypoxic-zone fibroblasts: Morphological characteristics and implications
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Okuno, Ryoko; Ito, Yuko; Eid, Nabil; Otsuki, Yoshinori; Kondo, Yoichi; Ueda, Koichi
    Keloid is a fibro-proliferative skin disorder with tumor-like behavior and dependence on anaerobic glycolysis (the Warburg effect), but its exact pathogenesis is unknown. Although autophagy is widely accepted as a lysosomal pathway for cell survival and cellular homeostasis (specifically upon exposure to stressors such as hypoxia), very few studies have investigated the involvement of autophagy and related glycolytic effectors in keloidogenesis. Here the authors examined the expression and cellular localization of autophagy proteins (LC3, pan-cathepsin), glycolytic markers (LDH, MCT1, MCT4) and the transcription factor HIF isoforms in human keloid samples using immunohistochemical analysis and double-labeling immunofluorescence methods. Based on H&E staining and expression of CD31, keloids were compartmentalized into hypoxic central and normoxic marginal zones. Vimentin-expressing fibroblasts in the central zone exhibited greater autophagy than their marginalzone counterparts, as evidenced by increased LC3 puncta formation and co-localization with lysosomal pan-cathepsin. LDH (a lactate stimulator), MCT4 (a lactate exporter) and HIF-1α expression levels were also higher in central-zone fibroblasts. Conversely, HIF-2α expression was upregulated in fibroblasts and endothelial cells of the peripheral zone, while MCT1 was expressed in both zones. Taken together, these observations suggest that upregulation of autophagy and glycolysis markers in keloid hypoxic-zone fibroblasts may indicate a prosurvival mechanism allowing the extrusion of lactate to marginal-zone fibroblasts via metabolic coupling. The authors believe this is the first report on differential expression of autophagic and glycolytic markers in keloid-zone fibroblasts. The study results indicate that autophagy inhibitors and MCT4 blockers may have therapeutic implications in keloid treatment