期刊
CELL DISCOVERY
卷 4, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41421-018-0014-5
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资金
- Singapore Ministry of Education under its Singapore Ministry of Academic Research Fund Tier 2 [MOE2010-T2-2-009, MOE2012-T2-1-014, MOE2014-T2-1-036, MOE2015-T1-001-034]
- A*STAR-NHG-NTU Skin Research Grant [SRG/14003]
- Lee Kong Chian School of Medicine, Nanyang Technological University (NTU) Start-Up Grant
- Region Midi-Pyrenees through the Chaire d'Excellence Pierre de Fermat
- Bonizzi-ThelerStiftung
- SERB-Department of Science & Technology (SERB-DST), Government of India [SB/S2/RJN-087/2014]
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 PPAR beta/delta in dermal fibrosis has not been elucidated. Thus, we generated a mouse strain with selective deletion of PPAR beta/delta 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 PPAR beta/delta in fibroblasts is an important signaling conduit integrating PPAR beta/delta and TGF beta 1-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.
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