Original Research Article
Decreased secretion of MMP by non-lesional late-stage scleroderma fibroblasts after selection via activation of the apoptotic fas-pathway
Article first published online: 19 APR 2011
Copyright © 2010 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 226, Issue 7, pages 1907–1914, July 2011
How to Cite
Chabaud, S., Corriveau, M.-P., Grodzicky, T., Senécal, J.-L., Chartier, S., Raymond, Y. and Moulin, V. J. (2011), Decreased secretion of MMP by non-lesional late-stage scleroderma fibroblasts after selection via activation of the apoptotic fas-pathway. J. Cell. Physiol., 226: 1907–1914. doi: 10.1002/jcp.22520
- Issue published online: 19 APR 2011
- Article first published online: 19 APR 2011
- Accepted manuscript online: 10 NOV 2010 12:00AM EST
- Manuscript Accepted: 25 OCT 2010
- Manuscript Received: 17 AUG 2010
- CIHR. Grant Number: MOP#77660
- Fondation du CHA-Hôpital Enfant Jésus/Saint-Sacrement
Our hypothesis is that the development of lesional areas of skin in patients with systemic sclerosis (SSc) originates from the selection of profibrotic cell subpopulations within their non-lesional skin areas, due to their greater resistance to apoptosis. Sensitivity to apoptosis of early-stage or late-stage SSc fibroblasts as well as of healthy cells was compared using extrinsic or intrinsic apoptotic pathway-inducers. Subpopulations of non-lesional SSc cells and healthy cells obtained after repeated Fas-induced apoptosis were compared with respect to their fibrotic parameters such as collagen and MMP secretion. Only late-stage lesional SSc cells were more resistant to Fas-induced apoptosis than their non-lesional counterparts isolated from the same patient. This result correlated with an increase in the levels of the anti-apoptotic proteins cFLIPs and cIAP in lesional cells compared to non-lesional cells. Healthy and non-lesional cell populations could be selected to generate a subpopulation that was more resistant to apoptosis. However, only the late-stage non-lesional SSc fibroblast populations showed a significant decrease in MMP secretion, one of parameters of the fibrosis. Our results show that resistance to apoptosis is an important characteristic of the late-stage lesional SSc fibroblast phenotype. We thus hypothesized that a selection of specific fibroblast subpopulations from late-stage non-lesional SSc skin areas could be at the origin of lesional populations. These cells should become independent of any exogenous stimuli and can induce or maintain SSc skin lesions. J. Cell. Physiol. 226: 1907–1914, 2011. © 2010 Wiley-Liss, Inc.