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2018
- doi: 10.1038/s41421-018-0014-5
- issn: 2056-5968
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M.K. Sng et al., « Selective deletion of PPARβ/δ in fibroblasts causes dermal fibrosis by attenuated LRG1 expression. », Serveur académique Lausannois, ID : 10.1038/s41421-018-0014-5
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Connective tissue diseases of the skin are characterized by excessive collagen deposition in the skin and internal organs. Fibroblasts play a pivotal role in the clinical presentation of these conditions. Nuclear receptor peroxisome-proliferator activated receptors (PPARs) are therapeutic targets for dermal fibrosis, but the contribution of the different PPAR subtypes are poorly understood. Particularly, the role of fibroblast PPARβ/δ in dermal fibrosis has not been elucidated. Thus, we generated a mouse strain with selective deletion of PPARβ/δ in the fibroblast (FSPCre- Pparb/d -/- ) and interrogated its epidermal and dermal transcriptome profiles. We uncovered a downregulated gene, leucine-rich alpha-2-glycoprotein-1 ( Lrg1 ), of previously unknown function in skin development and architecture. Our findings suggest that the regulation of Lrg1 by PPARβ/δ in fibroblasts is an important signaling conduit integrating PPARβ/δ and TGFβ1-signaling networks in skin health and disease. Thus, the FSPCre- Pparb/d -/- mouse model could serve as a novel tool in the current gunnery of animal models to better understand dermal fibrosis.