RNA sequencing identifies upregulated kyphoscoliosis peptidase and phosphatidic acid signaling pathways in muscle hypertrophy generated by transgenic expression of myostatin propeptide.

Abstract

Myostatin (MSTN), a member of the transforming growth factor-β superfamily, plays a crucial negative role in muscle growth. MSTN mutations or inhibitions can dramatically increase muscle mass in most mammal species. Previously, we generated a transgenic mouse model of muscle hypertrophy via the transgenic expression of the MSTN N-terminal propeptide cDNA under the control of the skeletal muscle-specific MLC1 promoter. Here, we compare the mRNA profiles between transgenic mice and wild-type littermate controls with a high-throughput RNA sequencing method. The results show that 132 genes were significantly differentially expressed between transgenic mice and wild-type control mice; 97 of these genes were up-regulated, and 35 genes were down-regulated in the skeletal muscle. Several genes that had not been reported to be involved in muscle hypertrophy were identified, including up-regulated myosin binding protein H (mybph), and zinc metallopeptidase STE24 (Zmpste24). In addition, kyphoscoliosis peptidase (Ky), which plays a vital role in muscle growth, was also up-regulated in the transgenic mice. Interestingly, a pathway analysis based on grouping the differentially expressed genes uncovered that cardiomyopathy-related pathways and phosphatidic acid (PA) pathways (Dgki, Dgkz, Plcd4) were up-regulated. Increased PA signaling may increase mTOR signaling, resulting in skeletal muscle growth. The findings of the RNA sequencing analysis help to understand the molecular mechanisms of muscle hypertrophy caused by MSTN inhibition.

• Authors: Yuanxin Miao, Jinzeng Yang, Zhong Xu, Lu Jing, Shuhong Zhao, Xinyun Li
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 16 Issue 4 Pg. 7976-94 (Apr 09 2015) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 25860951 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Cytoskeletal Proteins
• Membrane Proteins
• Muscle Proteins
• Myostatin
• Phosphatidic Acids
• RNA, Messenger
• KY protein, mouse
• Peptide Hydrolases
• Metalloendopeptidases
• Zmpste24 protein, mouse

Topics

• Animals
• Cytoskeletal Proteins (genetics)
• Down-Regulation (genetics)
• Hypertrophy (genetics)
• Male
• Membrane Proteins (genetics)
• Metalloendopeptidases (genetics)
• Mice
• Mice, Transgenic (genetics)
• Muscle Proteins (genetics)
• Muscle, Skeletal (metabolism)
• Muscular Diseases (genetics)
• Myostatin (genetics)
• Peptide Hydrolases
• Phosphatidic Acids (genetics)
• RNA, Messenger (genetics)
• Rats
• Sequence Analysis, RNA (methods)
• Signal Transduction (genetics)
• Up-Regulation (genetics)