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Published on: May 17, 2016
Lmod3 promotes myoblast differentiation and proliferation via the AKT and ERK pathways
Fei-Hu Lin1, Anmin Wang2, Wuhou Dai3
1State Key Laboratory of Genetic Engineering and National Center for International Research of Development and Disease, Fudan-Yale Center for Biomedical Research, Innovation Center for International Cooperation of Genetics and Development, Institute of Developmental Biology and Molecular Medicine, School of Life Sciences, Children's Hospital of Fudan University, Fudan University, Shanghai, China.
Abstract:
Mutations in the Lmod3 gene have been identified as a genetic cause of nemaline myopathy. However, the mechanism underlying this disease and the function of Lmod3 remain largely unknown. In this study, we found that Lmod3 knockdown in C2C12 cells impaired myoblast differentiation, whereas enforced Lmod3 expression enhanced such differentiation. We also discovered that myoblast proliferation was promoted by Lmod3 overexpression but impeded by its knockdown. Additionally, knockdown of Lmod3 led to apoptosis in myoblasts. Concurrently, forced Lmod3 expression in C2C12 cells contributed to activation of the AKT and ERK pathways during myoblast differentiation and proliferation, respectively. Conversely, knockdown of Lmod3 in C2C12 cells produced the opposite results. Furthermore, administration of IGF-1, a booster of both AKT and ERK pathways, partially rescued the inhibitory effect of Lmod3 knockdown on both differentiation and proliferation of C2C12 cells. These results suggest that Lmod3 promotes differentiation and proliferation of myoblasts through the AKT and ERK pathways, respectively.
Insights
The Lmod3 gene is crucial for muscle cell development. This study shows Lmod3 (Leucine-rich repeat-containing protein 3) promotes muscle cell differentiation and proliferation via AKT and ERK signaling pathways.
Area of Science:
- Muscle biology
- Cellular signaling
- Genetics
Background:
- Mutations in the Lmod3 gene are linked to nemaline myopathy.
- The precise function of Lmod3 and its role in muscle disease pathogenesis are not well understood.
Purpose of the Study:
- To investigate the role of Lmod3 in myoblast differentiation and proliferation.
- To elucidate the signaling pathways involved in Lmod3-mediated muscle cell regulation.
Main Methods:
- Utilized C2C12 myoblast cell line.
- Performed Lmod3 knockdown and overexpression experiments.
- Assessed myoblast differentiation, proliferation, and apoptosis.
- Analyzed AKT and ERK signaling pathway activation.
- Investigated the effect of IGF-1 administration.
Main Results:
- Lmod3 knockdown inhibited myoblast differentiation and proliferation, and induced apoptosis.
- Lmod3 overexpression enhanced myoblast differentiation and proliferation.
- Lmod3 modulated the activation of AKT and ERK pathways during differentiation and proliferation, respectively.
- IGF-1 partially rescued the negative effects of Lmod3 knockdown.
Conclusions:
- Lmod3 plays a significant role in promoting myoblast differentiation and proliferation.
- The AKT and ERK signaling pathways are key mediators of Lmod3's function in muscle cells.
- Lmod3 is a potential therapeutic target for muscle-related disorders.
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