Overexpression of Dnmt3a ameliorates diabetic muscle atrophy by modulating the Pten/Akt pathway

New Findings What is the central question of this study? Does Dnmt3a play a crucial role in regulating diabetic muscle atrophy? What is the main finding and its importance? Muscle atrophy is one of the major long‐term complications of diabetes mellitus. However, little is known about the molecular m...

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Bibliographic Details
Published in:Experimental physiology 2020-11, Vol.105 (11), p.1918-1927
Main Authors: Wang, Manfeng, Wu, Xiaowei, Gan, Lu, Teng, Zongyan, Zhang, Haijin, Zhang, Yina
Format: Article
Language:English
Subjects:
Akt
AKT protein
Animals
Atrophy
Diabetes
Diabetes mellitus
Diabetes Mellitus, Experimental - complications
Diabetes Mellitus, Experimental - metabolism
DNA Methyltransferase 3A - genetics
Dnmt3a
Epigenetics
Humans
Mice
muscle atrophy
Muscle Fibers, Skeletal - metabolism
Muscular Atrophy - etiology
Myoblasts
Myoblasts - metabolism
Myogenin
Myotubes
Palmitic acid
Phosphorylation
Proto-Oncogene Proteins c-akt - metabolism
Pten
PTEN Phosphohydrolase - metabolism
PTEN protein
Skeletal muscle
Streptozocin
Tibialis anterior muscle
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Summary:New Findings What is the central question of this study? Does Dnmt3a play a crucial role in regulating diabetic muscle atrophy? What is the main finding and its importance? Muscle atrophy is one of the major long‐term complications of diabetes mellitus. However, little is known about the molecular mechanism involved. In this paper, we demonstrated that Dnmt3a overexpression effectively improves the diabetic muscle health in mice and documented the underlying mechanisms. DNMT3A might become a promising target to prevent muscle atrophy in patients with diabetes. Muscle atrophy is one of the major long‐term complications of diabetes mellitus, which greatly affects the mobility of patients. Epigenetic processes mediated by DNA methyltransferases (DNMTs) play crucial roles in the locomotor system, but little is known about the functions of DNMTs in diabetic muscle atrophy. Here, we investigated the function of Dnmt3a in diabetic muscle atrophy and explored the mechanisms involved. Adeno‐associated virus AAV2 overexpressing Dnmt3a or its vector control was injected into the tibialis anterior muscle of streptozotocin‐induced diabetic mice. Muscle mass and muscle cross‐sectional area were used to evaluate muscle atrophy. In vitro, adeno‐associated virus AAV2 overexpressing Dnmt3a or its vector control was transfected into C2C12 myoblasts. Horse serum was used to induce differentiation and palmitate to stimulate the C2C12 myoblasts. The expressions of myogenic regulatory factors were examined by real‐time PCR and western blot analysis. Overexpression of Dnmt3a attenuated muscle atrophy in diabetic mice and promoted myotube formation of C2C12 myoblasts. Overexpression of Dnmt3a restored the expressions of myogenic regulatory factors atrogin‐1, MuRF1, Pax7, Myod1 and myogenin, both in vivo and in vitro. Moreover, overexpression of Dnmt3a activated the phosphorylation of Akt by inhibiting the activation of Pten. This study demonstrates that overexpression of Dnmt3a prevents diabetic muscle atrophy by modulating the Pten/Akt pathway.
ISSN:0958-0670
1469-445X
DOI:10.1113/EP088894