Sng, M.K., Chan, J.S.K., Teo, Z. et al. Selective deletion of PPARβ/δ in fibroblasts causes dermal fibrosis by attenuated LRG1 expression. Cell Discov 4, 15 (2018). https://doi.org/10.1038/s41421-018-0014-5
Abstract:
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.
License type:
http://creativecommons.org/licenses/by/4.0/
Funding Info:
This work is supported by the Singapore Ministry of Education under its Singapore Ministry of Academic Research Fund Tier 2 (MOE2010-T2- 2-009) to NST; (MOE2012-T2-1-014) to SC, (MOE2014-T2-1-036) to XW and WW, (MOE2015-T1-001-034) to WW and NST; and A*STAR-NHG-NTU Skin Research Grant (SRG/14003) to NST; Lee Kong Chian School of Medicine, Nanyang Technological University (NTU) Start-Up Grant, the Région Midi-Pyrénées through the Chaire d’Excellence Pierre de Fermat and the Bonizzi-Theler-Stiftung to WW. The authors are thankful to the Director, CSIR-NEIST, Jorhat for his support and SERB-Department of Science & Technology (SERB-DST), Government of India for providing the Ramanujan Fellowship (SB/S2/RJN-087/2014) to Dr. Mintu Pal.