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Published on: May 17, 2016
Slc2a6 regulates myoblast differentiation by targeting LDHB
Xuan Jiang1,2, Ninghan Feng1,3, Yizhou Zhou1
1Wuxi School of Medicine, Jiangnan University, 1800 Lihu Road, Wuxi, 214122, Jiangsu, China.
Background:
Type 2 diabetes mellitus is a global health problem. It often leads to a decline in the differentiation capacity of myoblasts and progressive loss of muscle mass, which in turn results in deterioration of skeletal muscle function. However, effective therapies against skeletal muscle diseases are unavailable.
Methods:
Skeletal muscle mass and differentiation ability were determined in db/+ and db/db mice. Transcriptomics and metabolomics approaches were used to explore the genetic mechanism regulating myoblast differentiation in C2C12 myoblasts.
Results:
In this study, the relatively uncharacterized solute carrier family gene Slc2a6 was found significantly up-regulated during myogenic differentiation and down-regulated during diabetes-induced muscle atrophy. Moreover, RNAi of Slc2a6 impaired the differentiation and myotube formation of C2C12 myoblasts. Both metabolomics and RNA-seq analyses showed that the significantly differentially expressed genes (e.g., LDHB) and metabolites (e.g., Lactate) during the myogenic differentiation of C2C12 myoblasts post-Slc2a6-RNAi were enriched in the glycolysis pathway. Furthermore, we show that Slc2a6 regulates the myogenic differentiation of C2C12 myoblasts partly through the glycolysis pathway by targeting LDHB, which affects lactic acid accumulation.
Conclusion:
Our study broadens the understanding of myogenic differentiation and offers the Slc2a6-LDHB axis as a potential therapeutic target for the treatment of diabetes-associated muscle atrophy. Video abstract.
Insights
Scientists identified Slc2a6 as crucial for muscle cell differentiation. Targeting the Slc2a6-LDHB pathway may treat muscle loss in type 2 diabetes.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- Type 2 diabetes mellitus (T2DM) is a global health issue.
- T2DM causes myoblast differentiation decline and muscle mass loss, impairing skeletal muscle function.
- Effective therapies for T2DM-associated muscle diseases are lacking.
Purpose of the Study:
- To investigate the genetic mechanisms underlying myoblast differentiation and T2DM-induced muscle atrophy.
- To identify novel therapeutic targets for diabetes-associated muscle wasting.
Main Methods:
- Comparative analysis of skeletal muscle in db/+ and db/db mice.
- Transcriptomic and metabolomic profiling of C2C12 myoblasts.
- RNA interference (RNAi) to assess Slc2a6 function.
Main Results:
- Slc2a6 expression is upregulated during myogenesis and downregulated in diabetes-induced muscle atrophy.
- Slc2a6 knockdown impairs C2C12 myoblast differentiation and myotube formation.
- Slc2a6 influences glycolysis and lactate production via LDHB, impacting myogenesis.
Conclusions:
- The Slc2a6-LDHB axis is a key regulator of myogenic differentiation.
- This pathway presents a potential therapeutic target for treating muscle atrophy in type 2 diabetes.
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