Dr. Leask's work was supported by the Scleroderma Society of Ontario and the Canadian Institutes of Health Research.
Skin Progenitor Cells Contribute to Bleomycin-Induced Skin Fibrosis
Article first published online: 25 FEB 2014
Copyright © 2014 by the American College of Rheumatology
Arthritis & Rheumatology
Volume 66, Issue 3, pages 707–713, March 2014
How to Cite
Liu, S., Herault, Y., Pavlovic, G. and Leask, A. (2014), Skin Progenitor Cells Contribute to Bleomycin-Induced Skin Fibrosis. Arthritis & Rheumatology, 66: 707–713. doi: 10.1002/art.38276
- Issue published online: 25 FEB 2014
- Article first published online: 25 FEB 2014
- Accepted manuscript online: 18 NOV 2013 11:20AM EST
- Manuscript Accepted: 7 NOV 2013
- Manuscript Received: 20 MAY 2013
The origin of the cells that contribute to skin fibrosis is unclear. We undertook the present study to assess the contribution of Sox2-expressing skin progenitor cells to bleomycin-induced scleroderma.
Scleroderma was induced, by bleomycin administration, in wild-type mice and in mice in which CCN2 was deleted from Sox2-expressing cells. Lineage tracing analysis was performed to assess whether cells expressing Sox2 are recruited to fibrotic lesions in response to bleomycin-induced scleroderma.
In response to bleomycin, Sox2-positive/α-smooth muscle actin–positive cells were recruited to fibrotic tissue. CCN2–conditional knockout mice in which CCN2 was deleted from Sox2-expressing cells exhibited resistance to bleomycin-induced skin fibrosis. Collectively, these results indicate that CCN2 is required for the recruitment of progenitor cells and that CCN2-expressing progenitor cells are essential for bleomycin-induced skin fibrosis. Lineage tracing analysis using mice in which a tamoxifen-dependent Cre recombinase was expressed under the control of the Sox2 promoter confirmed that progenitor cells were recruited to the fibrotic lesion in response to bleomycin, and that this did not occur in CCN2-knockout mice. The ability of serum to induce α-smooth muscle actin expression in skin progenitor cells required the presence of CCN2.
Sox2-positive skin progenitor cells are required in order for bleomycin-induced skin fibrosis to occur, and CCN2 is required for the recruitment of these cells to the fibrotic lesion. Targeting stem cell recruitment or CCN2 may therefore represent a useful therapeutic approach in combating fibrotic skin disease.