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Selective deletion of PPAR beta/delta in fibroblasts causes dermal fibrosis by attenuated LRG1 expression
- Source :
- Cell Discovery, Cell Discovery, 2018, 4, ⟨10.1038/s41421-018-0014-5⟩, Cell Discovery, Vol 4, Iss 1, Pp 1-16 (2018), Cell Discovery (4), . (2018), Cell discovery, vol. 4, pp. 15
- Publication Year :
- 2018
- Publisher :
- HAL CCSD, 2018.
-
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.
- Subjects :
- 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)
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Cell Discovery, Cell Discovery, 2018, 4, ⟨10.1038/s41421-018-0014-5⟩, Cell Discovery, Vol 4, Iss 1, Pp 1-16 (2018), Cell Discovery (4), . (2018), Cell discovery, vol. 4, pp. 15
- Accession number :
- edsair.doi.dedup.....4aeba379b0856a59b339eea783f2354f