Metabolic regulation of dermal fibroblasts contributes to skin extracellular matrix homeostasis and fibrosis

Nature Metabolism
Xiao ZhaoFei-Fei Liu

Abstract

Extracellular matrix (ECM) homeostasis is essential for normal tissue function, and its disruption by iatrogenic injury, trauma, or disease results in fibrosis. Skin ECM homeostasis is maintained by a complex process that involves an integration of cytokine and environmental mediators. However, it is unclear, in both normal and disease states, how these multifactorial processes converge to shift ECM homeostasis towards accumulation or degradation. Here we show a consistent downregulation in fatty acid oxidation (FAO) and upregulation of glycolysis in fibrotic skin and in normal skin with abundant ECM. Perturbation of glycolysis and FAO pathway enzymes reveals their reciprocal effects in ECM upregulation and downregulation, respectively. Increasing peroxisome proliferator-activated receptor (PPAR) signalling, an inducer of the FAO pathway, generates a catabolic fibroblast phenotype characterised by inhibition of ECM transcription and enhanced ECM internalization and lysosomal degradation. In contrast, suppression of glycolysis inhibits ECM gene transcription and protein levels, independently of an intact FAO pathway or PPAR signalling. Moreover, we show that CD36, a multifunctional fatty acid transporter, connects the metabolic ...Continue Reading

References

Jul 1, 1984·International Journal of Radiation Oncology, Biology, Physics·H B Stone
Jun 1, 1993·Journal of Cellular Physiology·C A McCulloch, G C Knowles
Sep 19, 2001·The Journal of Clinical Investigation·M FebbraioR L Silverstein
Sep 5, 2002·Biochemical and Biophysical Research Communications·Motohide IsonoFuad N Ziyadeh
Sep 11, 2003·The Lancet Oncology·Helen B StoneWilliam H McBride
Aug 19, 2004·American Journal of Physiology. Renal Physiology·Debra F HigginsVolker H Haase
Oct 19, 2007·The Journal of Investigative Dermatology·Annette S VincentKim P Wong
May 23, 2009·Science·Matthew G Vander HeidenCraig B Thompson
Jan 1, 2011·Journal of Radiology Case Reports·Amar Mehta, Todd M Blodgett
Oct 26, 2013·Nature Protocols·F Ann RanFeng Zhang
Oct 15, 2014·Nature Reviews. Nephrology·Helena M KokTri Q Nguyen
Oct 15, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Pengxuan ZhangJin-Ao Duan
Jun 6, 2015·Cell Research·Beth Kelly, Luke A J O'Neill
Aug 19, 2015·American Journal of Respiratory and Critical Care Medicine·Na XieGang Liu
Dec 15, 2015·Bioinformatics·Petr SmirnovBenjamin Haibe-Kains
Feb 24, 2016·PPAR Research·Luca VanellaIgnazio Barbagallo
Jul 4, 2016·Trends in Endocrinology and Metabolism : TEM·Sara LovisaRaghu Kalluri
Jan 1, 2015·Cell Death Discovery·M W KhanP Chakrabarti
Apr 30, 2017·Respiratory Research·Aurélien JustetBruno Crestani

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Citations

Jul 11, 2020·ELife·Allison N LauMatthew G Vander Heiden
Aug 5, 2020·JCI Insight·Roohi VinaikMarc G Jeschke
Sep 1, 2020·Experimental Dermatology·Zhuzhen ZhangPhilipp E Scherer
Jul 9, 2020·American Journal of Respiratory Cell and Molecular Biology·Kamran AtabaiMichael J Podolsky
May 15, 2020·Journal of Digestive Diseases·Simon Bos, Debby Laukens
Jan 1, 2019·Nature Metabolism·Joshua D Rabinowitz, Gökhan M Mutlu
Sep 25, 2019·Nature Reviews. Drug Discovery·Xiao ZhaoFei-Fei Liu
Apr 17, 2020·Biomolecules·Thanh-Diep LyIsabel Faust
Oct 15, 2019·Frontiers in Immunology·Leonhard von MeyennChristoph Schlapbach
Sep 23, 2020·Current Rheumatology Reports·Hanlin YinQingran Yan
Aug 1, 2019·Nature Reviews. Drug Discovery·Chirag H PatelJonathan D Powell
Dec 1, 2020·The FEBS Journal·Hussein FarahSimon W Jones
Feb 27, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jung Wook HuhMark W Dewhirst
Jan 13, 2021·Molecular Diagnosis & Therapy·Wanlu ShenLechun Lyu
Jan 5, 2021·The FEBS Journal·Robert B Hamanaka, Gökhan M Mutlu
Dec 18, 2020·Frontiers in Cell and Developmental Biology·Ying YeYongtian Lu
Jan 28, 2020·Trends in Cell Biology·Shohini Ghosh-ChoudharyToren Finkel
Feb 26, 2021·Journal of Hepatology·Helene GilgenkrantzSophie Lotersztajn
Mar 13, 2021·Circulation·Jorge OllerMaría Mittelbrunn
Jan 25, 2020·Biochemical and Biophysical Research Communications·Thanh-Diep LyIsabel Faust
Apr 4, 2021·International Journal of Molecular Sciences·Gali Epstein ShochetDavid Shitrit
Apr 7, 2021·The Journal of Experimental Medicine·Rami BecharaSarah L Gaffen
May 11, 2021·Journal of Biomedical Science·Angelo Giuseppe CondorelliDaniele Castiglia
May 16, 2021·Acta Pharmacologica Sinica·Yuan-Yuan ChenSen Zhang
May 25, 2021·Trends in Endocrinology and Metabolism : TEM·John Henderson, Steven O'Reilly
Jun 3, 2021·International Journal of Molecular Sciences·Veronica RomanoAlessandro Arcucci
Jun 13, 2021·Journal of Materials Science. Materials in Medicine·Jesús A Claudio-RizoJuan J Becerra-Rodriguez
Jul 7, 2021·Drug Discovery Today·Leyla Norouzi-Barough, Ardeshir Bayat
Aug 14, 2021·Cell Metabolism·Sabine A EmingEdward J Pearce

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Methods Mentioned

BETA
pharmacotherapy
PCR
flow cytometry
ELISA
enzyme-linked immunosorbent assay
RNA-seq
X-Ray
sedation
chip
Profiler

Software Mentioned

LUMI Bioconductor
gplots
FASTQC
SeQC
Inveon Research Workplace
Cufflinks
BLAST
Mass Profiler Professional
CummeRBund
PharmacoGx package

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