GDF8 Contributes to Liver Fibrogenesis and Concomitant Skeletal Muscle Wasting
Abstract
:1. Introduction
2. Materials and Methods
2.1. Approval of Animal Studies
2.2. Carbon Tetrachloride Liver Fibrosis Model
2.3. Skeletal Muscle Injury Model
2.4. Gene Expression Analysis
2.5. Protein Quantification
2.6. Histology and Immunohistochemistry
2.7. Human Liver Sample Collection
2.8. ActRIIA-Fc and ActRIIB-Fc Proteins and Antibodies
2.9. Body Composition
2.10. Cell Culture and In Vitro Assays
2.11. Data Analysis and Presentation
3. Results
3.1. Acute Liver Injury Induces Rapid and Negative Responses in Skeletal Muscle
3.2. Neutralization of ActRIIB Ligands but Not Activin A May Prevent the Initiation of Liver Injury-Induced Muscle Atrophy
3.3. Neutralization of ActRIIB Ligands Prevents Chronic Liver Injury-Induced Muscle Atrophy Independent of Gender
3.4. Neutralization of ActRIIB Ligands Reverses Chronic Liver Injury-Induced Muscle Atrophy
3.5. Injured Liver Produces Gdf8 in Both Humans and Mice
3.6. Neutralization of Gdf8 Prevents Chronic Liver Injury and Concomitant Muscle Mass Loss
3.7. Neutralization of Gdf8 Reverses Chronic Liver Injury and Concomitant Muscle Mass Loss
3.8. Liver Injury Negatively Affects Muscle Regeneration, Which Is Prohibited by Neutralization of ActRIIB Ligands
3.9. Exogenous Gdf8 Disrupts Muscle Regeneration, Mimicking Liver Injury
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Culver, A.; Hamang, M.; Wang, Y.; Jiang, H.; Yanum, J.; White, E.; Gawrieh, S.; Vuppalanchi, R.K.; Chalasani, N.P.; Dai, G.; et al. GDF8 Contributes to Liver Fibrogenesis and Concomitant Skeletal Muscle Wasting. Biomedicines 2023, 11, 1909. https://doi.org/10.3390/biomedicines11071909
Culver A, Hamang M, Wang Y, Jiang H, Yanum J, White E, Gawrieh S, Vuppalanchi RK, Chalasani NP, Dai G, et al. GDF8 Contributes to Liver Fibrogenesis and Concomitant Skeletal Muscle Wasting. Biomedicines. 2023; 11(7):1909. https://doi.org/10.3390/biomedicines11071909
Chicago/Turabian StyleCulver, Alexander, Matthew Hamang, Yan Wang, Huaizhou Jiang, Jennifer Yanum, Emily White, Samer Gawrieh, Raj K. Vuppalanchi, Naga P. Chalasani, Guoli Dai, and et al. 2023. "GDF8 Contributes to Liver Fibrogenesis and Concomitant Skeletal Muscle Wasting" Biomedicines 11, no. 7: 1909. https://doi.org/10.3390/biomedicines11071909