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Updated: Jul 22, 2025
Author Spotlight: Advanced Integrated Model for Sepsis-Induced Myopathy and Single-Cell Metabolic Analysis
Published on: June 14, 2024
MicroRNA-140 is not involved in sepsis-induced muscle atrophy
Jaehoon Shin1, Shigeru Miyaki2, Hiroshi Asahara3
1Laboratory of Muscle Biology, Faculty of Sport Sciences, Waseda University, Saitama, Japan.
Abstract:
Sepsis is a life-threatening inflammatory response to infection, often accompanied by skeletal muscle atrophy. A previous study demonstrated that the administration of microRNA-140 (miR-140) attenuated lipopolysaccharide (LPS)-induced muscle atrophy, whereas miR-140 knockdown with siRNA promoted atrophy. Therefore, we investigated whether miR-140 is involved in LPS-induced muscle atrophy using a genetic model, miR-140-/- mice. We found that a single injection of LPS induced atrophy both in slow-twitch and fast-twitch muscles. The muscle weights and fiber cross-sectional areas were significantly reduced in both the wild-type (WT) and miR-140-/- mice, with no difference between genotypes. The expression of several proteolysis markers, muscle-specific RING-finger 1 (MuRF1) and MAFbx/atrogin-1, increased in both groups after LPS injection. The ubiquitinated proteins in the miR-140-/- mice were similar to those in the WT mice. Therefore, the deletion of miR-140 did not affect LPS-induced muscle atrophy.NEW & NOTEWORTHY We used miR-140-/- mice to determine the function of miR-140 in LPS-induced skeletal muscle atrophy. To our knowledge, this study is the first to examine slow-twitch muscles in LPS-induced muscle wasting after miR-140 manipulation.
Insights
MicroRNA-140 (miR-140) does not influence lipopolysaccharide (LPS)-induced skeletal muscle atrophy. Deleting miR-140 in mice did not alter muscle wasting or proteolysis markers following LPS exposure.
Area of Science:
- Biochemistry
- Physiology
- Molecular Biology
Background:
- Sepsis triggers a severe inflammatory response, often leading to skeletal muscle atrophy.
- Previous research suggested microRNA-140 (miR-140) plays a role in mitigating lipopolysaccharide (LPS)-induced muscle wasting.
Purpose of the Study:
- To investigate the role of miR-140 in LPS-induced skeletal muscle atrophy using a genetic knockout model.
- To analyze the impact of miR-140 deletion on both slow-twitch and fast-twitch muscle groups.
Main Methods:
- Utilized miR-140 knockout (-/-) mice and wild-type (WT) littermates.
- Administered a single dose of lipopolysaccharide (LPS) to induce sepsis-like conditions.
- Assessed muscle weight, fiber cross-sectional area, and expression of key proteolysis markers (MuRF1, MAFbx/atrogin-1).
Main Results:
- LPS injection induced significant muscle atrophy in both WT and miR-140-/- mice.
- No significant differences in muscle atrophy or proteolysis marker expression were observed between genotypes.
- Ubiquitinated protein levels were comparable between WT and miR-140-/- mice after LPS administration.
Conclusions:
- The absence of miR-140 does not exacerbate or protect against LPS-induced skeletal muscle atrophy.
- miR-140 is not a critical factor in the development of muscle wasting following LPS exposure in this model.
- This study provides novel insights into slow-twitch muscle responses in LPS-induced muscle wasting concerning miR-140 manipulation.
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