Dupuytren’s disease (DD) is a fibro-proliferative disorder characterised by progressive palmar fascia fibrosis. Despite known risk factors and associations, the pathogenesis of DD remains unclear.
We have previously identified an embryonic stem cell (ESC)–like population in the endothelium of the microvessels around the cords and nodules of DD. We have also demonstrated that this primitive population expresses components of the renin-angiotensin system (RAS). Cathepsins B, D and G are proteases that contribute to RAS bypass loops. We postulate that cathepsins B, D and G are expressed in DD.
3,3-Diaminobezidine (DAB) immunohistochemical (IHC) staining for cathepsins B, D and G, was performed on formalin-fixed paraffin-embedded cords (n=10) and nodules (n=10) of DD samples. Immunofluorescent (IF) IHC staining was utilised to demonstrate co-expression of these cathepsins with ESC markers. Transcriptional activation for these cathepsins were assessed by NanoString gene expression analysis on snap-frozen cords (n=3) and nodules (n=3) of DD samples.
IHC staining demonstrated the expression of cathepsins B, D and G in the cords and nodules of DD. Cathepsins B and D were localised extensively to the (i) tissue core; (ii) OCT4+ and ACE+ endothelium and (iii) the smooth muscle layer, of the microvessels. Limited expression of cathepsin G on the microvessels was observed. Transcriptional expression of cathepsins B, D and G was confirmed by NanoString analysis.
Discussion and Conclusion:
This study demonstrates the expression of cathepsins B, D and G in both the cords and nodules of DD. The expression of cathepsins B and D by the endothelium of the microvessels that also expressed the ESC marker OCT4, and ACE, a component of the RAS, suggests the presence of potential bypass loops for the RAS. These novel findings infer a crucial role for RAS and stem cells in the pathogenesis of DD.