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Programmed cell death in nodular palmar fibromatosis (Morbus Dupuytren)
B Wilutzky1, A Berndt, D Katenkamp
1Institute of Pathology, Friedrich Schiller University Jena, Germany.
Abstract:
The regular loss of cellularity during involutional phase of nodular palmar fibromatosis (Morbus Dupuytren) indicates a regulated process known as programmed cell death (apoptosis). Using the TUNEL method apoptosis-related DNA fragmentation is detected in numerous cells as a characteristic feature of fibromatosis noduli of involutional phase. By means of double labelling technique, alpha-smooth muscle actin immunohistochemistry and TUNEL method for apoptosis, it is demonstrated that the cells which underwent apoptotosis are myofibroblasts. As anticipated, the antidote to apoptosis bcl-2 is not detected in involutional phase, but neither it is evidenced in proliferative phase. Immunohistochemically, Fas/APO-1 is shown to be existent in a very small number of fibroblasts in involutional phase. However, in view of the high number of TUNEL-stained cells a significance in regulating apoptosis in nodular palmar fibromatosis seems improbable. Taking into account that the development of the fibromatosis noduli, the expression of myofibroblast phenotype, basement membrane formation and growth factor expression including TGF beta culminates in involutional phase the initiation of apoptotic cell death can be discussed in relation to these growth factors and matrix protein action and the programmed cell death may be considered as the final step of myofibroblast phenotype evolution.
Insights
Programmed cell death (apoptosis) is key in Dupuytren
Area of Science:
- Cell Biology
- Pathology
- Dermatology
Background:
- Nodular palmar fibromatosis, also known as Dupuytren's disease, involves cellular changes during its involutional phase.
- The loss of cellularity suggests a regulated process, specifically programmed cell death (apoptosis).
Purpose of the Study:
- To investigate the role and mechanisms of apoptosis in the involutional phase of Dupuytren's disease.
- To identify the specific cell types undergoing apoptosis and their relation to myofibroblast differentiation.
Main Methods:
- Utilized the TUNEL assay to detect DNA fragmentation indicative of apoptosis.
- Employed double labeling techniques combining alpha-smooth muscle actin immunohistochemistry with TUNEL staining.
- Assessed the expression of apoptosis-related proteins, including bcl-2 and Fas/APO-1.
Main Results:
- TUNEL staining revealed significant DNA fragmentation in numerous cells during the involutional phase of fibromatosis noduli.
- Apoptotic cells were identified as myofibroblasts, characterized by alpha-smooth muscle actin expression.
- The apoptosis inhibitor bcl-2 was not detected in either the proliferative or involutional phases; Fas/APO-1 expression was minimal.
Conclusions:
- Apoptosis is a significant, regulated process in the involutional phase of Dupuytren's disease, primarily affecting myofibroblasts.
- The observed apoptosis may be linked to growth factors and matrix protein actions, representing a terminal stage of myofibroblast evolution.
- Standard apoptosis regulatory proteins like bcl-2 and Fas/APO-1 appear to play a limited role in this specific context.