1. Selective deletion of PPAR beta/delta in fibroblasts causes dermal fibrosis by attenuated LRG1 expression
- Author
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Ya Lin Tnay, Terri Phua, Mintu Pal, Shunsuke Chiba, Ming Keat Sng, Jia Peng Chen, Jonathan Wei Kiat Wee, Jeremy Soon Kiat Chan, Benny Meng Kiat Tong, Walter Wahli, Eddie Han Pin Tan, Nguan Soon Tan, Ziqiang Teo, Nikki Jun Ning Koh, Xuan Rui Ng, Xiaomeng Wang, Pengcheng Zhu, Chek Kun Tan, Lee Kong Chian School of Medicine, Nanyang Technological University (NTU), School of Biological Sciences, Department of Microbiology, Tumor and Cell Biology, Ajouter cet établissement, CSIR North East Inst Sci & Technol, Biol Sci & Technol Div, Jorhat 785006, Assam, India, Partenaires INRAE, University College of London [London] (UCL), Singapore Eye Research Institute [Singapore] (SERI), Institute of Molecular and Cell Biology, University of Tartu, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), KK Research Centre, KK Women’s and Children’s Hospital (KKH), 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, Lee Kong Chian School of Medicine (LKCMedicine), School of Physical and Mathematical Sciences, and Sng, Ming Keat
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0301 basic medicine ,[SDV]Life Sciences [q-bio] ,Peroxisome proliferator-activated receptor ,Connective tissue ,Dermal Fibrosis ,Biochemistry ,Article ,03 medical and health sciences ,Selective Deletion ,Genetics ,medicine ,lcsh:QH573-671 ,Receptor ,Fibroblast ,Molecular Biology ,Gene ,chemistry.chemical_classification ,integumentary system ,lcsh:Cytology ,Chemistry ,Cell Biology ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Nuclear receptor ,LRG1 ,Function (biology) - 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.
- Published
- 2018