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 p...

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Main Authors: Kirin Tan, MB ChB, Helen D. Brasch, BMedSc, MBChB, Bede van Schaijik, BTech (Hons), James R. Armstrong, MBBS, MD, Reginald W. Marsh, PhD, Paul F. Davis, PhD, Swee T. Tan, MBBS, PhD, Tinte Itinteang, MBBS, PhD
Format: Article
Language:English
Published: Wolters Kluwer 2018-02-01
Series:Plastic and Reconstructive Surgery, Global Open
Online Access:http://journals.lww.com/prsgo/fulltext/10.1097/GOX.0000000000001686
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author Kirin Tan, MB ChB
Helen D. Brasch, BMedSc, MBChB
Bede van Schaijik, BTech (Hons)
James R. Armstrong, MBBS, MD
Reginald W. Marsh, PhD
Paul F. Davis, PhD
Swee T. Tan, MBBS, PhD
Tinte Itinteang, MBBS, PhD
author_facet Kirin Tan, MB ChB
Helen D. Brasch, BMedSc, MBChB
Bede van Schaijik, BTech (Hons)
James R. Armstrong, MBBS, MD
Reginald W. Marsh, PhD
Paul F. Davis, PhD
Swee T. Tan, MBBS, PhD
Tinte Itinteang, MBBS, PhD
author_sort Kirin Tan, MB ChB
collection DOAJ
description 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.
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spelling doaj.art-0238606b8cc94ab79b89b65e3b38d23d2022-12-22T02:58:26ZengWolters KluwerPlastic and Reconstructive Surgery, Global Open2169-75742018-02-0162e168610.1097/GOX.0000000000001686201802000-00009Expression and Localization of Cathepsins B, D, and G in Dupuytren’s DiseaseKirin Tan, MB ChB0Helen D. Brasch, BMedSc, MBChB1Bede van Schaijik, BTech (Hons)2James R. Armstrong, MBBS, MD3Reginald W. Marsh, PhD4Paul F. Davis, PhD5Swee T. Tan, MBBS, PhD6Tinte Itinteang, MBBS, PhD7From the *Gillies McIndoe Research Institute, Wellington, New Zealand; †Wellington Regional Plastic, Maxillofacial & Burns Unit, Hutt Hospital, Wellington, New Zealand; and ‡University of Auckland, Auckland, New Zealand.From the *Gillies McIndoe Research Institute, Wellington, New Zealand; †Wellington Regional Plastic, Maxillofacial & Burns Unit, Hutt Hospital, Wellington, New Zealand; and ‡University of Auckland, Auckland, New Zealand.From the *Gillies McIndoe Research Institute, Wellington, New Zealand; †Wellington Regional Plastic, Maxillofacial & Burns Unit, Hutt Hospital, Wellington, New Zealand; and ‡University of Auckland, Auckland, New Zealand.From the *Gillies McIndoe Research Institute, Wellington, New Zealand; †Wellington Regional Plastic, Maxillofacial & Burns Unit, Hutt Hospital, Wellington, New Zealand; and ‡University of Auckland, Auckland, New Zealand.From the *Gillies McIndoe Research Institute, Wellington, New Zealand; †Wellington Regional Plastic, Maxillofacial & Burns Unit, Hutt Hospital, Wellington, New Zealand; and ‡University of Auckland, Auckland, New Zealand.From the *Gillies McIndoe Research Institute, Wellington, New Zealand; †Wellington Regional Plastic, Maxillofacial & Burns Unit, Hutt Hospital, Wellington, New Zealand; and ‡University of Auckland, Auckland, New Zealand.From the *Gillies McIndoe Research Institute, Wellington, New Zealand; †Wellington Regional Plastic, Maxillofacial & Burns Unit, Hutt Hospital, Wellington, New Zealand; and ‡University of Auckland, Auckland, New Zealand.From the *Gillies McIndoe Research Institute, Wellington, New Zealand; †Wellington Regional Plastic, Maxillofacial & Burns Unit, Hutt Hospital, Wellington, New Zealand; and ‡University of Auckland, Auckland, New Zealand.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.http://journals.lww.com/prsgo/fulltext/10.1097/GOX.0000000000001686
spellingShingle Kirin Tan, MB ChB
Helen D. Brasch, BMedSc, MBChB
Bede van Schaijik, BTech (Hons)
James R. Armstrong, MBBS, MD
Reginald W. Marsh, PhD
Paul F. Davis, PhD
Swee T. Tan, MBBS, PhD
Tinte Itinteang, MBBS, PhD
Expression and Localization of Cathepsins B, D, and G in Dupuytren’s Disease
Plastic and Reconstructive Surgery, Global Open
title Expression and Localization of Cathepsins B, D, and G in Dupuytren’s Disease
title_full Expression and Localization of Cathepsins B, D, and G in Dupuytren’s Disease
title_fullStr Expression and Localization of Cathepsins B, D, and G in Dupuytren’s Disease
title_full_unstemmed Expression and Localization of Cathepsins B, D, and G in Dupuytren’s Disease
title_short Expression and Localization of Cathepsins B, D, and G in Dupuytren’s Disease
title_sort expression and localization of cathepsins b d and g in dupuytren s disease
url http://journals.lww.com/prsgo/fulltext/10.1097/GOX.0000000000001686
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