Wouter R P H van de Worp1, Jan Theys2, Ardy van Helvoort1,3, Ramon C J Langen1. 1. Department of Respiratory Medicine, NUTRIM. 2. Department of Radiation Oncology, GROW, Maastricht University Medical Center+, Maastricht. 3. Nutricia Research, Nutricia Advanced Medical Nutrition, Utrecht, the Netherlands.
Abstract
PURPOSE OF REVIEW: To provide an overview and describe the mode of action of miRNAs recently implicated in muscle atrophy, and discuss the challenges to explore their potential as putative therapeutic targets in cachexia. RECENT FINDINGS: Recent work showed differentially expressed miRNAs in skeletal muscle of patients with cachexia-associated diseases. Studies using experimental models revealed miRNA regulation of the anabolic IGF-1 and catabolic TGF- β/myostatin pathways, and downstream protein synthesis and proteolysis signaling in control of muscle mass. SUMMARY: Cachexia is a complex metabolic condition associated with progressive body weight loss, wasting of skeletal muscle mass and decrease in muscle strength. MiRNAs play a central role in post-transcriptional gene regulation by targeting mRNAs, thereby coordinating and fine-tuning many cellular processes. MiRNA expression profiling studies of muscle biopsies have revealed differentially expressed miRNAs in patients with low muscle mass or cachexia. Evaluation in experimental models has revealed muscle atrophy, inhibition of protein synthesis and activation of proteolysis in response to modulation of specific miRNAs, termed 'atromiRs' in this review. These exciting findings call for further studies aimed at exploring the conservation of differentially expressed miRNAs across diseases accompanied by cachexia, identification of miRNA clusters and targets involved in muscle atrophy, and probing whether these miRNAs might be potential therapeutic targets for cachexia.
PURPOSE OF REVIEW: To provide an overview and describe the mode of action of miRNAs recently implicated in muscle atrophy, and discuss the challenges to explore their potential as putative therapeutic targets in cachexia. RECENT FINDINGS: Recent work showed differentially expressed miRNAs in skeletal muscle of patients with cachexia-associated diseases. Studies using experimental models revealed miRNA regulation of the anabolic IGF-1 and catabolic TGF- β/myostatin pathways, and downstream protein synthesis and proteolysis signaling in control of muscle mass. SUMMARY:Cachexia is a complex metabolic condition associated with progressive body weight loss, wasting of skeletal muscle mass and decrease in muscle strength. MiRNAs play a central role in post-transcriptional gene regulation by targeting mRNAs, thereby coordinating and fine-tuning many cellular processes. MiRNA expression profiling studies of muscle biopsies have revealed differentially expressed miRNAs in patients with low muscle mass or cachexia. Evaluation in experimental models has revealed muscle atrophy, inhibition of protein synthesis and activation of proteolysis in response to modulation of specific miRNAs, termed 'atromiRs' in this review. These exciting findings call for further studies aimed at exploring the conservation of differentially expressed miRNAs across diseases accompanied by cachexia, identification of miRNA clusters and targets involved in muscle atrophy, and probing whether these miRNAs might be potential therapeutic targets for cachexia.
Authors: Ismita Chhetri; Julie E A Hunt; Jeewaka R Mendis; Stephen D Patterson; Zudin A Puthucheary; Hugh E Montgomery; Benedict C Creagh-Brown Journal: Trials Date: 2019-07-24 Impact factor: 2.279
Authors: Wouter R P H van de Worp; Annemie M W J Schols; Anne-Marie C Dingemans; Céline M H Op den Kamp; Juliette H R J Degens; Marco C J M Kelders; Susan Coort; Henry C Woodruff; Gueorqui Kratassiouk; Annick Harel-Bellan; Jan Theys; Ardy van Helvoort; Ramon C J Langen Journal: J Cachexia Sarcopenia Muscle Date: 2019-12-11 Impact factor: 12.910