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Published on: July 15, 2014
TLR2 deficiency attenuates skeletal muscle atrophy in mice
Dae-Sung Kim1, Hye-Na Cha2, Hye Jun Jo2
1Department of Orthopedic Surgery, College of Medicine, Yeungnam University, Daegu 705-717, South Korea.
Abstract:
Oxidative stress and inflammation are associated with skeletal muscle atrophy. Because the activation of toll-like receptor (TLR) 2 induces oxidative stress and inflammation, TLR2 may be directly linked to skeletal muscle atrophy. This study examined the role of TLR2 in skeletal muscle atrophy in wild-type (WT) and TLR2 knockout (KO) mice. Immobilization for 2 weeks increased the expression of cytokine genes and the levels of carbonylated proteins and nitrotyrosine in the skeletal muscle, but these increases were lower in the TLR2 KO mice. Muscle weight loss and a reduction in treadmill running times induced by immobilization were also attenuated in TLR2 KO mice. Furthermore, immobilization increased the protein levels of forkhead box O 1/3, atrogin-1 and muscle ring finger 1 in the WT mice, which was attenuated in TLR2 KO mice. In addition, immobilization-associated increases in ubiquitinated protein levels were lower in the TLR2 KO mice. Immobilization increased the phosphorylation of Akt and p70S6K similarly in WT and KO mice. Furthermore, cardiotoxin injection into the skeletal muscle increased the protein levels of atrogin-1, interleukin-6, and nitrotyrosine and increased the levels of ubiquitinated proteins, although these levels were increased to a lesser extent in TLR2 KO mice. These results suggest that TLR2 is involved in skeletal muscle atrophy, and the inhibition of TLR2 offers a potential target for preventing skeletal muscle atrophy.
Insights
Toll-like receptor (TLR) 2 activation contributes to skeletal muscle atrophy by increasing oxidative stress and inflammation. Inhibiting TLR2 in mice attenuated muscle atrophy markers, suggesting TLR2 as a therapeutic target.
Area of Science:
- Muscle physiology
- Immunology
- Molecular biology
Background:
- Skeletal muscle atrophy is linked to oxidative stress and inflammation.
- Toll-like receptor (TLR) 2 activation can induce oxidative stress and inflammation.
- TLR2's direct role in skeletal muscle atrophy requires investigation.
Purpose of the Study:
- To investigate the role of TLR2 in skeletal muscle atrophy.
- To compare skeletal muscle atrophy in wild-type (WT) and TLR2 knockout (KO) mice.
Main Methods:
- Mice (WT and TLR2 KO) underwent immobilization for 2 weeks.
- Skeletal muscle was analyzed for cytokine gene expression, protein carbonylation, nitrotyrosine, and ubiquitinated proteins.
- Muscle weight, running times, and key atrophy-related proteins (FOXO1/3, atrogin-1, MuRF1) were assessed.
- Cardiotoxin-induced muscle injury model was used to further evaluate TLR2's role.
Main Results:
- Immobilization increased atrophy markers in WT mice, with attenuated increases in TLR2 KO mice.
- Muscle weight loss and reduced running times were less severe in TLR2 KO mice.
- TLR2 deficiency reduced immobilization-induced increases in atrophy-related proteins and ubiquitinated proteins.
- Cardiotoxin-induced increases in atrogin-1, IL-6, and nitrotyrosine were lower in TLR2 KO mice.
Conclusions:
- TLR2 plays a significant role in skeletal muscle atrophy.
- TLR2 inhibition may be a viable strategy for preventing muscle atrophy.
