MiR-206 Attenuates Denervation-Induced Skeletal Muscle Atrophy in Rats Through Regulation of Satellite Cell Differentiation via TGF-β1, Smad3, and HDAC4 Signaling
| Autor: | Ming-Huan Fu, Hu-Yuan Qiao, Bing-sheng Liang, Wenbin Li, Jian Wei, Zhi Chen, Gang Li, Qiang Kai Huang |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Satellite Cells Skeletal Muscle Cellular differentiation Biology Real-Time Polymerase Chain Reaction Histone Deacetylases Myoblasts Rats Sprague-Dawley Transforming Growth Factor beta1 Random Allocation 03 medical and health sciences Gastrocnemius muscle Atrophy Internal medicine medicine Animals RNA Messenger Smad3 Protein Muscle Skeletal Denervation Muscle Denervation Animal Study Skeletal muscle Cell Differentiation General Medicine medicine.disease Sciatic Nerve Muscle atrophy Rats MicroRNAs Muscular Atrophy 030104 developmental biology Endocrinology medicine.anatomical_structure Sciatic nerve medicine.symptom Signal Transduction |
| Zdroj: | Medical Science Monitor : International Medical Journal of Experimental and Clinical Research |
| ISSN: | 1643-3750 |
| DOI: | 10.12659/msm.897909 |
| Popis: | BACKGROUND Denervation-induced skeletal muscle atrophy results in significant biochemical and physiological changes potentially leading to devastating outcomes including increased mortality. Effective treatments for skeletal muscle diseases are currently not available. Muscle-specific miRNAs, such as miR-206, play an important role in the regulation of muscle regeneration. The aim of the present study was to examine the beneficial effects of miR-206 treatment during the early changes in skeletal muscle atrophy, and to study the underlying signaling pathways in a rat skeletal muscle atrophy model. MATERIAL AND METHODS The rat denervation-induced skeletal muscle atrophy model was established. miRNA-206 was overexpressed with or without TGF-β1 inhibitor in the rats. The mRNA and protein expression of HDAC4, TGF-β1, and Smad3 was determined by real-time PCR and western blot. The gastrocnemius muscle cross-sectional area and relative muscle mass were measured. MyoD1, TGF-β1, and Pax7 were determined by immunohistochemical staining. RESULTS After sciatic nerve surgical transection, basic muscle characteristics, such as relative muscle weight, deteriorated continuously during a 2-week period. Injection of miR-206 (30 μg/rat) attenuated morphological and physiological deterioration of muscle characteristics, prevented fibrosis effectively, and inhibited the expression of TGF-β1 and HDAC4 as assessed 2 weeks after denervation. Moreover, miR-206 treatment increased the number of differentiating (MyoD1+/Pax7+) satellite cells, thereby protecting denervated muscles from atrophy. Interestingly, the ability of miR-206 to govern HDAC4 expression and to attenuate muscle atrophy was weakened after pharmacological blockage of the TGF-b1/Smad3 axis. CONCLUSIONS TGF-β1/Smad3 signaling pathway is one of the crucial signaling pathways by which miR-206 counteracts skeletal muscle atrophy by affecting proliferation and differentiation of satellite cells. miR-206 may be a potential target for development of a new strategy for treatment of patients with early denervation-induced skeletal muscle atrophy. |
| Databáze: | OpenAIRE |
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