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Theranostics, Published 2025-3-21; 15(10):4579-4592 | doi:10.7150/thno.108280
ROS-responsive MnO2 mesoporous hydrogel to modulate liver-muscle crosstalk and mitigate NAFLD-associated sarcopenia via exosomal miR-582-5p delivery
Songling Jiang4#, Tae Min Kim2,3#, Sung Young Park2,3, Eun-Jung Jin1,4
1Department of Biomedical Materials Science, Graduate school of JABA, Wonkwang University, Iksan, Jeonbuk State, 54538, Republic of Korea.
2Department of IT and Energy Convergence (BK21 FOUR), Korea National University of Transportation, Chungju 27469, Republic of Korea.
3Department of Chemical and Biological Engineering, Korea National University of Transportation, Chungju 27469, Republic of Korea.
4Integrated Omics Institute, Wonkwang University, Iksan, Jeonbuk State, 54538, Republic of Korea.
1Department of Biomedical Materials Science, Graduate school of JABA, Wonkwang University, Iksan, Jeonbuk State, 54538, Republic of Korea.
2Department of IT and Energy Convergence (BK21 FOUR), Korea National University of Transportation, Chungju 27469, Republic of Korea.
3Department of Chemical and Biological Engineering, Korea National University of Transportation, Chungju 27469, Republic of Korea.
4Integrated Omics Institute, Wonkwang University, Iksan, Jeonbuk State, 54538, Republic of Korea.
#These authors contributed equally.
Corresponding authors: Sung Young Park, Eun-Jung Jin
Abstract
Background: The interrelation between non-alcoholic fatty liver disease (NAFLD) and sarcopenia has emerged as a significant concern due to its systemic impact on metabolic health. However, therapeutic approaches targeting the liver-muscle axis remain underdeveloped. Oxidative stress and inflammatory pathways are key mediators of this crosstalk, exacerbating disease progression. This study aims to develop a reactive oxygen species (ROS)-responsive MnO2 mesoporous PD (HA) hydrogel to modulate this axis and investigate its therapeutic efficacy in NAFLD-associated sarcopenia.
Methods: MnO2 mesoporous PD (HA) hydrogels were synthesized with ROS-sensitive properties and characterized for rheological, fluorescence, and conductivity responses. A HepG2-C2C12 co-culture model mimicked the NAFLD-muscle wasting interplay, while high-fat diet (HFD)-induced NAFLD mouse models were used for in vivo evaluations. Cellular stress markers, exosomal miR-582-5p signaling, and atrogenic pathways were assessed using immunofluorescence, qRT-PCR, and histological analyses.
Results: Pathway analysis of HFD-induced NAFLD showed upregulation of lipid metabolism and inflammatory signaling, promoting muscle atrophy via exosomal miR-582-5p. The MnO2 mesoporous hydrogel significantly reduced oxidative stress and inflammation in the HepG2-C2C12 co-culture. In vivo, hydrogel implantation in HFD mice mitigated hepatic fibrosis, reduced ROS accumulation, preserved muscle fiber integrity, and downregulated atrogenic markers.
Conclusions: The MnO2 mesoporous PD (HA) hydrogel presents a dual-targeting therapeutic strategy for NAFLD and sarcopenia by attenuating oxidative stress and modulating liver-muscle axis signaling. These findings provide a foundation for innovative interventions targeting metabolic comorbidities.
Methods: MnO2 mesoporous PD (HA) hydrogels were synthesized with ROS-sensitive properties and characterized for rheological, fluorescence, and conductivity responses. A HepG2-C2C12 co-culture model mimicked the NAFLD-muscle wasting interplay, while high-fat diet (HFD)-induced NAFLD mouse models were used for in vivo evaluations. Cellular stress markers, exosomal miR-582-5p signaling, and atrogenic pathways were assessed using immunofluorescence, qRT-PCR, and histological analyses.
Results: Pathway analysis of HFD-induced NAFLD showed upregulation of lipid metabolism and inflammatory signaling, promoting muscle atrophy via exosomal miR-582-5p. The MnO2 mesoporous hydrogel significantly reduced oxidative stress and inflammation in the HepG2-C2C12 co-culture. In vivo, hydrogel implantation in HFD mice mitigated hepatic fibrosis, reduced ROS accumulation, preserved muscle fiber integrity, and downregulated atrogenic markers.
Conclusions: The MnO2 mesoporous PD (HA) hydrogel presents a dual-targeting therapeutic strategy for NAFLD and sarcopenia by attenuating oxidative stress and modulating liver-muscle axis signaling. These findings provide a foundation for innovative interventions targeting metabolic comorbidities.
논문정보
- Research article
- 2025년 03월 (BRIC 등록일 2025-03-27)
- 국내 연구진
- 의약학 > 분자세포의학
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