Selective deletion of PPARβ/δ in fibroblasts causes dermal fibrosis by attenuated LRG1 expression.

Détails

Ressource 1Télécharger: s41421-018-0014-5.pdf (3545.31 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_2F8C4A54B142
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Selective deletion of PPARβ/δ in fibroblasts causes dermal fibrosis by attenuated LRG1 expression.
Périodique
Cell discovery
Auteur(s)
Sng M.K., Chan JSK, Teo Z., Phua T., Tan EHP, Wee JWK, Koh NJN, Tan C.K., Chen J.P., Pal M., Tong BMK, Tnay Y.L., Ng X.R., Zhu P., Chiba S., Wang X., Wahli W., Tan N.S.
ISSN
2056-5968 (Print)
ISSN-L
2056-5968
Statut éditorial
Publié
Date de publication
2018
Peer-reviewed
Oui
Volume
4
Pages
15
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
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- <i>Pparb/d</i> <sup>-/-</sup> ) and interrogated its epidermal and dermal transcriptome profiles. We uncovered a downregulated gene, leucine-rich alpha-2-glycoprotein-1 ( <i>Lrg1</i> ), of previously unknown function in skin development and architecture. Our findings suggest that the regulation of <i>Lrg1</i> 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- <i>Pparb/d</i> <sup>-/-</sup> mouse model could serve as a novel tool in the current gunnery of animal models to better understand dermal fibrosis.

Pubmed
Web of science
Open Access
Oui
Création de la notice
14/04/2018 12:01
Dernière modification de la notice
20/08/2019 14:14
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