serval:BIB_2F8C4A54B142
Selective deletion of PPARβ/δ in fibroblasts causes dermal fibrosis by attenuated LRG1 expression.
10.1038/s41421-018-0014-5
000429191400001
29619245
Sng
M.K.
author
Chan
JSK
author
Teo
Z.
author
Phua
T.
author
Tan
EHP
author
Wee
JWK
author
Koh
NJN
author
Tan
C.K.
author
Chen
J.P.
author
Pal
M.
author
Tong
BMK
author
Tnay
Y.L.
author
Ng
X.R.
author
Zhu
P.
author
Chiba
S.
author
Wang
X.
author
Wahli
W.
author
Tan
N.S.
author
article
2018
Cell discovery
2056-5968
2056-5968
journal
4
15
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.
eng
60_published
true
peer-reviewed
Publication types: Journal Article
Publication Status: epublish
University of Lausanne
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