title: Investigation of the Expression of Myogenic Transcription Factors, microRNAs and Muscle-Specific E3 Ubiquitin Ligases in the Medial Gastrocnemius and Soleus Muscles following Peripheral Nerve Injury.
abstract: Despite surgical innovation, the sensory and motor outcome after a peripheral nerve injury remains incomplete. One contributing factor to the poor outcome is prolonged denervation of the target organ, leading to apoptosis of both mature myofibres and satellite cells with subsequent replacement of the muscle tissue with fibrotic scar and adipose tissue. In this study, we investigated the expression of myogenic transcription factors, muscle specific microRNAs and muscle-specific E3 ubiquitin ligases at several time points following denervation in two different muscles, the gastrocnemius (containing predominantly fast type fibres) and soleus (slow type) muscles, since these molecules may influence the degree of atrophy following denervation. Both muscles exhibited significant atrophy (compared with the contra-lateral sides) at 7 days following either a nerve transection or crush injury. In the crush model, the soleus muscle showed significantly increased muscle weights at days 14 and 28 which was not the case for the gastrocnemius muscle which continued to atrophy. There was a significantly more pronounced up-regulation of MyoD expression in the denervated soleus muscle compared with the gastrocnemius muscle. Conversely, myogenin was more markedly elevated in the gastrocnemius versus soleus muscles. The muscles also showed significantly contrasting transcriptional regulation of the microRNAs miR-1 and miR-206. MuRF1 and Atrogin-1 showed the highest levels of expression in the denervated gastrocnemius muscle. This study provides further insights regarding the intracellular regulatory molecules that generate and maintain distinct patterns of gene expression in different fibre types following peripheral nerve injury.
authors.affiliation: Department of Integrative Medical Biology, Section of Anatomy, Umeå University, Umeå, Sweden.|Department of Surgical & Perioperative Sciences, Section of Hand and Plastic Surgery, Umeå University, Umeå, Sweden.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Wiberg
authors.affiliation: Department of Integrative Medical Biology, Section of Anatomy, Umeå University, Umeå, Sweden.|Department of Surgical & Perioperative Sciences, Section of Hand and Plastic Surgery, Umeå University, Umeå, Sweden.
authors.forename: Samuel
authors.initials: S
authors.lastname: Jonsson
authors.affiliation: Department of Integrative Medical Biology, Section of Anatomy, Umeå University, Umeå, Sweden.
authors.forename: Liudmila N
authors.initials: LN
authors.lastname: Novikova
authors.affiliation: Department of Integrative Medical Biology, Section of Anatomy, Umeå University, Umeå, Sweden.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Kingham
mesh_terms: D000818:Animals; D005260:Female; D005786:Gene Expression Regulation; D035683:MicroRNAs / Q000096:biosynthesis*; D009124:Muscle Proteins / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D018006:Myogenic Regulatory Factors / Q000096:biosynthesis*; D059348:Peripheral Nerve Injuries / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044843:SKP Cullin F-Box Protein Ligases / Q000096:biosynthesis*; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis*
chemical_list: C542191:MIRN1 microRNA, rat; D035683:MicroRNAs; D009124:Muscle Proteins; D018006:Myogenic Regulatory Factors; D000070584:Tripartite Motif Proteins; C522220:mirn206 microRNA, rat; C486692:Fbxo32 protein, rat; D044843:SKP Cullin F-Box Protein Ligases; C499086:Trim63 protein, rat; D044767:Ubiquitin-Protein Ligases