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Arthritis Rheum. 2009 Sep;60(9):2822-9. doi: 10.1002/art.24761.

Loss of peroxisome proliferator-activated receptor gamma in mouse fibroblasts results in increased susceptibility to bleomycin-induced skin fibrosis.

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University of Western Ontario, London, Ontario, Canada.



There is increasing evidence that the transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma) plays an important role in controlling cell differentiation, and that PPARgamma ligands can modify inflammatory and fibrotic responses. The aim of the present study was to examine the role of PPARgamma in a mouse model of skin scleroderma, in which mice bearing a fibroblast-specific deletion of PPARgamma were used.


Cutaneous sclerosis was induced by subcutaneous injection of bleomycin, while untreated control groups were injected with phosphate buffered saline. Mice bearing a fibroblast-specific deletion of PPARgamma were investigated for changes in dermal thickness, inflammation, collagen content, and the number of alpha-smooth muscle actin-positive cells. The quantity of the collagen-specific amino acid hydroxyproline was also measured. In addition, the effect of PPARgamma deletion on transforming growth factor beta1 (TGFbeta1) signaling in the fibroblasts was investigated.


Bleomycin treatment induced marked cutaneous thickening and fibrosis in all treated mice. Deletion of PPARgamma resulted in enhanced susceptibility to bleomycin-induced skin fibrosis, as indicated by increases in all measures of skin fibrosis and enhanced sensitivity of fibroblasts to TGFbeta1 in PPAR-deficient mice.


These results indicate that PPARgamma suppresses fibrogenesis. Specific agonists of PPARgamma may therefore alleviate the extent of the development of cutaneous sclerosis.

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