title: MicroRNA-208b progressively declines after spinal cord injury in humans and is inversely related to myostatin expression.
abstract: The effects of long-term physical inactivity on the expression of microRNAs involved in the regulation of skeletal muscle mass in humans are largely unknown. MicroRNAs are short, noncoding RNAs that fine-tune target expression through mRNA degradation or by inhibiting protein translation. Intronic to the slow, type I, muscle fiber type genes MYH7 and MYH7b, microRNA-208b and microRNA-499-5p are thought to fine-tune the expression of genes important for muscle growth, such as myostatin. Spinal cord injured humans are characterized by both skeletal muscle atrophy and transformation toward fast-twitch, type II fibers. We determined the expression of microRNA-208b, microRNA-499-5p, and myostatin in human skeletal muscle after complete cervical spinal cord injury. We also determined whether these microRNAs altered myostatin expression in rodent skeletal muscle. A progressive decline in skeletal muscle microRNA-208b and microRNA-499-5p expression occurred in humans during the first year after spinal cord injury and with long-standing spinal cord injury. Expression of myostatin was inversely correlated with microRNA-208b and microRNA-499-5p in human skeletal muscle after spinal cord injury. Overexpression of microRNA-208b in intact mouse skeletal muscle decreased myostatin expression, whereas microRNA-499-5p was without effect. In conclusion, we provide evidence for an inverse relationship between expression of microRNA-208b and its previously validated target myostatin in humans with severe skeletal muscle atrophy. Moreover, we provide direct evidence that microRNA-208b overexpression decreases myostatin gene expression in intact rodent muscle. Our results implicate that microRNA-208b modulates myostatin expression and this may play a role in the regulation of skeletal muscle mass following spinal cord injury.
authors.affiliation: Department of Molecular Medicine and Surgery, Section for Integrative Physiology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Hanneke
authors.initials: H
authors.lastname: Boon
authors.affiliation: Department of Molecular Medicine and Surgery, Section for Integrative Physiology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Rasmus J O
authors.initials: RJ
authors.lastname: Sjögren
authors.affiliation: Department of Molecular Medicine and Surgery, Section for Integrative Physiology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Julie
authors.initials: J
authors.lastname: Massart
authors.affiliation: Department of Molecular Medicine and Surgery, Section for Integrative Physiology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Brendan
authors.initials: B
authors.lastname: Egan
authors.affiliation: Section for Spinal Cord Injury, Sunnaas Rehabilitation Hospital, Nesoddtangen, Norway Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Emil
authors.initials: E
authors.lastname: Kostovski
authors.affiliation: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway Department of Hematology, Oslo University Hospital, Oslo, Norway.
authors.forename: Per O
authors.initials: PO
authors.lastname: Iversen
authors.affiliation: Section for Spinal Cord Injury, Sunnaas Rehabilitation Hospital, Nesoddtangen, Norway.
authors.forename: Nils
authors.initials: N
authors.lastname: Hjeltnes
authors.affiliation: Department of Molecular Medicine and Surgery, Section for Integrative Physiology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Chibalin
authors.affiliation: Department of Molecular Medicine and Surgery, Section for Integrative Physiology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Widegren
authors.affiliation: Department of Molecular Medicine and Surgery, Section for Integrative Physiology, Karolinska Institutet, Stockholm, Sweden Juleen.Zierath@ki.se.
authors.forename: Juleen R
authors.initials: JR
authors.lastname: Zierath
keywords: MicroRNA; skeletal muscle; spinal cord injury