PPARβ/δ Agonism Upregulates Forkhead Box A2 to Reduce Inflammation in C2C12 Myoblasts and in Skeletal Muscle

International Journal of Molecular Sciences
Wendy Wen Ting PhuaNguan Soon Tan

Abstract

Daily activities expose muscles to innumerable impacts, causing accumulated tissue damage and inflammation that impairs muscle recovery and function, yet the mechanism modulating the inflammatory response in muscles remains unclear. Our study suggests that Forkhead box A2 (FoxA2), a pioneer transcription factor, has a predominant role in the inflammatory response during skeletal muscle injury. FoxA2 expression in skeletal muscle is upregulated by fatty acids and peroxisome proliferator-activated receptors (PPARs) but is refractory to insulin and glucocorticoids. Using PPARβ/δ agonist GW501516 upregulates FoxA2, which in turn, attenuates the production of proinflammatory cytokines and reduces the infiltration of CD45+ immune cells in two mouse models of muscle inflammation, systemic LPS and intramuscular injection of carrageenan, which mimic localized exercise-induced inflammation. This reduced local inflammatory response limits tissue damage and restores muscle tetanic contraction. In line with these results, a deficiency in either PPARβ/δ or FoxA2 diminishes the action of the PPARβ/δ agonist GW501516 to suppress an aggravated inflammatory response. Our study suggests that FoxA2 in skeletal muscle helps maintain homeostasis, ac...Continue Reading

References

Jul 1, 1995·Medicine and Science in Sports and Exercise·J G Tidball
Feb 19, 2002·Journal of Neuroscience Methods·Mohan K SapruBayer Thimmapaya
Aug 20, 2002·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Robert A FrostCharles H Lang
Jul 17, 2003·The Journal of Clinical Investigation·Christian WolfrumMarkus Stoffel
Sep 23, 2003·Proceedings of the National Academy of Sciences of the United States of America·Christian WolfrumMarkus Stoffel
Nov 25, 2003·Advances in Physiology Education·Susan V Brooks
Aug 26, 2004·PLoS Biology·Yong-Xu WangRonald M Evans
Apr 30, 2005·Trends in Pharmacological Sciences·Joel P BergerPeter T Meinke
Aug 16, 2005·Cell Metabolism·Liping ZhangKlaus H Kaestner
Feb 10, 2006·Annals of the New York Academy of Sciences·Xiuping YuRobert J Matusik
Apr 8, 2006·Physiological Reviews·Béatrice DesvergneWalter Wahli
Apr 28, 2006·Journal of Anatomy·Hechmi ToumiThomas M Best
Aug 16, 2006·Cellular and Molecular Life Sciences : CMLS·J R Friedman, K H Kaestner
Oct 3, 2007·Cell Metabolism·Nan GaoKlaus H Kaestner
Dec 23, 2008·Exercise and Sport Sciences Reviews·Bénédicte ChazaudFabrice Chretien
Apr 18, 2009·Experimental Cell Research·Alberto MalerbaMaurizio David Baroni
May 14, 2009·The Journal of Clinical Investigation·Zhaoyu LiKlaus H Kaestner
Feb 24, 2010·BMC Developmental Biology·Robert B WhitePeter S Zammit
May 21, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gang ChenJeffrey A Whitsett
Jul 19, 2011·The Journal of Clinical Investigation·Emidio E PistilliTejvir S Khurana
Nov 8, 2011·Genes & Development·Kenneth S Zaret, Jason S Carroll
Apr 21, 2012·Advances in Nutrition·Anastasia Georgiadi, Sander Kersten
Sep 7, 2012·Advances in Clinical Chemistry·Anastassios PhilippouMichael Koutsilieris
Mar 30, 2013·Journal of Applied Physiology·Maria L Urso
Jul 17, 2013·Clinical Cases in Mineral and Bone Metabolism : the Official Journal of the Italian Society of Osteoporosis, Mineral Metabolism, and Skeletal Diseases·Alessandra PratesiMauro Di Bari
Mar 13, 2014·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Richard Wa Mackenzie, Bradley T Elliott
Oct 9, 2014·Calcified Tissue International·Walter R Frontera, Julien Ochala
Jul 29, 2015·Advances in Experimental Medicine and Biology·Sue C Bodine, J David Furlow
Oct 11, 2015·Bone·Svenia Schnyder, Christoph Handschin
Jan 20, 2017·Cell Death & Disease·Jeremy Soon Kiat ChanNguan Soon Tan
May 4, 2017·Cell Metabolism·Weiwei FanRonald M Evans
Apr 18, 2018·Journal of Orthopaedic Translation·Wenjun Yang, Ping Hu
May 12, 2018·International Journal of Molecular Sciences·Wendy Wen Ting PhuaNguan Soon Tan

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Citations

Oct 1, 2021·Cell Death and Differentiation·Xiang-Qian GaoKun Wang

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Methods Mentioned

BETA
immunoprecipitation
transfection
PCR
chIP
Assay

Clinical Trials Mentioned

NCT01524406

Software Mentioned

R
Goseq package

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