Selective deletion of PPAR?/? in fibroblasts causes dermal fibrosis by attenuated LRG1 expression.

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 PPAR?/? in dermal fibrosis has not been elucidated. Thus, we generated a mouse strain with selective deletion of PPAR?/? 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?/? in fibroblasts is an important signaling conduit integrating PPAR?/? and TGF?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.

SUBMITTER: Sng MK 

PROVIDER: S-EPMC5880809 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature