Research article summary (published 30 Aug 2009):

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

Full Abstract

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: These results indicate that PPARgamma suppresses fibrogenesis. Specific agonists of PPARgamma may therefore alleviate the extent of the development of cutaneous sclerosis.

Author information

Author/s: Kapoor, Mohit (M); McCann, Matthew (M); Liu, Shangxi (S); Huh, Kun (K); Denton, Christopher P (CP); Abraham, David J (DJ); Leask, Andrew (A);

Affiliation: University of Western Ontario, London, Ontario, Canada.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Arthritis and rheumatism (Arthritis Rheum), published in United States. (Language: eng)

Reference: 2009-Sep; vol 60 (issue 9) : pp 2822-9

Dates: Created 2009/09/21; Completed 2009/10/19;

PMID: 19714649, status: MEDLINE (last retrieval date: 10/19/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Actins - metabolism Animals Bleomycin Cells, Cultured Disease Models, Animal Fibroblasts - metabolism; pathology Fibrosis Gene Deletion Genetic Predisposition to Disease - genetics

Genetic Predisposition to Disease - genetics Mice Mice, Knockout PPAR gamma - agonists; genetics; metabolism Scleroderma, Systemic - genetics; metabolism; pathology Signal Transduction - physiology Skin - pathology Smad3 Protein - metabolism Transforming Growth Factor beta1 - metabolism

Associated Chemicals: Actins (0) ; PPAR gamma (0) ; Smad3 Protein (0) ; Smad3 protein, mouse (0) ; Transforming Growth Factor beta1 (0) ; Bleomycin (11056-06-7)

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