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

Kirin Tan1, Helen D Brasch1, Bede van Schaijik1

  • 1Gillies McIndoe Research Institute, Wellington, New Zealand; Wellington Regional Plastic, Maxillofacial & Burns Unit, Hutt Hospital, Wellington, New Zealand; and University of Auckland, Auckland, New Zealand.

Insights

Cathepsins B and D are found in Dupuytren

Area of Science:

  • Vascular Biology
  • Cellular Biology
  • Pathogenesis Research

Background:

  • The exact cause of Dupuytren's disease (DD) is unknown.
  • A population of cells resembling embryonic stem cells (ESCs) in microvessel endothelium expresses renin-angiotensin system (RAS) components.
  • This study explores if these primitive cells express cathepsins B, D, and G, which may form RAS bypass loops.

Purpose of the Study:

  • To investigate the expression and localization of cathepsins B, D, and G in Dupuytren's disease tissues.
  • To determine if these cathepsins are associated with the embryonic stem cell-like population in microvessels.
  • To assess the functional activity of cathepsins and their potential role in RAS bypass loops in DD pathogenesis.

Main Methods:

  • Immunohistochemistry (IHC) using 3,3-Diaminobenzidine and immunofluorescence to detect cathepsins B, D, and G and ESC markers.
  • Western blotting and NanoString analysis to assess protein and gene expression of cathepsins.
  • Enzymatic activity assays to confirm the functional activity of cathepsins.

Main Results:

  • Cathepsins B, D, and G were expressed in DD cords and nodules at both gene and protein levels (cathepsin G protein expression was limited).
  • Cathepsins B and D were highly abundant in the endothelium and smooth muscle of microvessels, co-localizing with OCT4+/angiotensin converting enzyme+ cells.
  • Cathepsin G was primarily found in stromal tryptase+ cells, not on microvessels, and cathepsins B and D showed functional enzymatic activity.

Conclusions:

  • Cathepsins B, D, and G are present in Dupuytren's disease tissues.
  • Cathepsins B and D are localized to a primitive endothelial cell population, suggesting a role in RAS bypass.
  • Cathepsin G localizes to mast cells, indicating a distinct role, potentially also contributing to RAS bypass mechanisms.
Abstract

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