Por favor, use este identificador para citar o enlazar este ítem: DOI: 10.14670/HH-18-005

Título: Upregulation of autophagy and glycolysis markers in keloid hypoxic-zone fibroblasts: Morphological characteristics and implications
Fecha de publicación: 2018
Editorial: Universidad de Murcia. Departamento de Biología Celular e Histología
Cita bibliográfica: Histology and Histopathology, Vol.33, nº10, (2018)
ISSN: 1699-5848
Materias relacionadas: CDU::6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncología
Palabras clave: Autophagy
Warburg effect
Resumen: 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
Autor/es principal/es: Okuno, Ryoko
Ito, Yuko
Eid, Nabil
Otsuki, Yoshinori
Kondo, Yoichi
Ueda, Koichi
URI: http://hdl.handle.net/10201/120340
DOI: DOI: 10.14670/HH-18-005
Tipo de documento: info:eu-repo/semantics/article
Número páginas / Extensión: 13
Derechos: info:eu-repo/semantics/openAccess
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Aparece en las colecciones:Vol.33,nº10 (2018)

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