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Expression and Localization of Cathepsins B, D, and G in Dupuytren’s Disease

BACKGROUND: The pathogenesis of Dupuytren’s disease (DD) remains unclear. An embryonic stem cell (ESC)–like population in the endothelium of the microvessels around tissues that expresses components of the renin-angiotensin system (RAS) has been reported. This study investigated if this primitive po...

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Detalles Bibliográficos
Autores principales: Tan, Kirin, Brasch, Helen D., van Schaijik, Bede, Armstrong, James R., Marsh, Reginald W., Davis, Paul F., Tan, Swee T., Itinteang, Tinte
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Wolters Kluwer Health 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5865920/
https://www.ncbi.nlm.nih.gov/pubmed/29616179
http://dx.doi.org/10.1097/GOX.0000000000001686
Descripción
Sumario:BACKGROUND: The pathogenesis of Dupuytren’s disease (DD) remains unclear. An embryonic stem cell (ESC)–like population in the endothelium of the microvessels around tissues that expresses components of the renin-angiotensin system (RAS) has been reported. This study investigated if this primitive population expresses cathepsins B, D, and G, that contribute to RAS bypass loops. METHODS: 3,3-Diaminobenzidine immunohistochemical (IHC) staining for cathepsins B, D, and G was performed on sections of formalin-fixed paraffin-embedded DD cords (n = 10) and nodules (n = 10). Immunofluorescence IHC staining was utilized to demonstrate co-expression of these cathepsins with ESC markers. Protein and gene expression of these cathepsins was investigated in snap-frozen DD cords (n = 3) and nodules (n = 3) by Western blotting and NanoString analysis, respectively. Enzymatic activity of these cathepsins was investigated by enzymatic activity assays. RESULTS: 3,3-Diaminobenzidine IHC staining demonstrated expression of cathepsins B, D, and G in DD cords and nodules. Gene expression of cathepsins B, D, and G was confirmed by NanoString analysis. Western blotting confirmed expression of cathepsins B and D, but not cathepsin G. Immunofluorescent IHC staining demonstrated high abundance of cathepsins B and D on the OCT4(+)/angiotensin converting enzyme(+) endothelium and the smooth muscle layer of the microvessels. Cathepsin G was localized to trypase(+) cells within the stroma in DD cords and nodules with limited expression on the microvessels. Enzyme activity assays demonstrated functional activity of cathepsins B and D. CONCLUSIONS: Cathepsins B, D, and G were expressed in the DD tissues, with cathepsins B and D localized to the primitive population in the endothelium of the microvessels, whereas cathepsin G was localized to phenotypic mast cells, suggesting the presence of bypass loops for the RAS.