title: Exercise, skeletal muscle and inflammation: ARE-binding proteins as key regulators in inflammatory and adaptive networks.
abstract: The role of inflammation in skeletal muscle adaptation to exercise is complex and has hardly been elucidated so far. While the acute inflammatory response to exercise seems to promote skeletal muscle training adaptation and regeneration, persistent, low-grade inflammation, as seen in a multitude of chronic diseases, is obviously detrimental. The regulation of cytokine production in skeletal muscle cells has been relatively well studied, yet little is known about the compensatory and anti-inflammatory mechanisms that resolve inflammation and restore tissue homeostasis. One important strategy to ensure sequential, timely and controlled resolution of inflammation relies on the regulated stability of mRNAs encoding pro-inflammatory mediators. Many key transcripts in early immune responses are characterized by the presence of AU-rich elements (AREs) in the 3'-untranslated regions of their mRNAs, allowing efficient fine-tuning of gene expression patterns at the post-transcriptional level. AREs exert their function by recruiting particular RNA-binding proteins, resulting, in most cases, in de-stabilization of the target transcripts. The best-characterized ARE-binding proteins are HuR, CUGBP1, KSRP, AUF1, and the three ZFP36 proteins, especially TTP/ZFP36. Here, we give a general introduction into the role of inflammation in the adaptation of skeletal muscle to exercise. Subsequently, we focus on potential roles of ARE-binding proteins in skeletal muscle tissue in general and specifically exercise-induced skeletal muscle remodeling. Finally, we present novel data suggesting a specific function of TTP/ZFP36 in exercise-induced skeletal muscle plasticity.
authors.affiliation: Department of Sports Medicine, Medical Clinic, Eberhard-Karls-University Tübingen, Tübingen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Beiter
authors.affiliation: Division of Pathobiochemistry and Clinical Chemistry, Department of Internal Medicine IV, Eberhard-Karls-University Tübingen, Tübingen, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Hoene
authors.affiliation: Department of Sports Medicine, Medical Clinic, Eberhard-Karls-University Tübingen, Tübingen, Germany.
authors.forename: Frauke
authors.initials: F
authors.lastname: Prenzler
authors.affiliation: Department of Sports Medicine, Institute of Sports Sciences, Justus-Liebig University Gießen, Gießen, Germany.
authors.forename: Frank C
authors.initials: FC
authors.lastname: Mooren
authors.affiliation: Division of Sports and Rehabilitation Medicine, Ulm University Medical Center, Ulm, Germany.
authors.forename: Jürgen M
authors.initials: JM
authors.lastname: Steinacker
authors.affiliation: Division of Pathobiochemistry and Clinical Chemistry, Department of Internal Medicine IV, Eberhard-Karls-University Tübingen, Tübingen, Germany.|German Center for Diabetes Research (DZD).
authors.forename: Cora
authors.initials: C
authors.lastname: Weigert
authors.affiliation: Department of Sports Medicine, Medical Clinic, Eberhard-Karls-University Tübingen, Tübingen, Germany.
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Nieß
authors.affiliation: Department of Sports Medicine, Medical Clinic, Eberhard-Karls-University Tübingen, Tübingen, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Munz
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000222:Adaptation, Physiological / Q000235:genetics / Q000502:physiology; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000502:physiology; D015444:Exercise / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000502:physiology; D009119:Muscle Contraction / Q000235:genetics / Q000502:physiology; D009124:Muscle Proteins / Q000502:physiology*; D018482:Muscle, Skeletal / Q000254:growth & development / Q000502:physiology*; D010805:Physical Conditioning, Animal / Q000502:physiology; D012323:RNA Processing, Post-Transcriptional; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000502:physiology*; D012038:Regeneration / Q000502:physiology; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; D016207:Cytokines; D018836:Inflammation Mediators; D009124:Muscle Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins
keywords: AU-rich element binding protein (ABP); HuR.; ZFP36/TTP; cachexia; exercise; inflammation; mRNA stability; regeneration; resolution of inflammation; skeletal muscle