Myeloid-Specific STAT3 Deletion Aggravates Liver Fibrosis in Mice Fed a Methionine- and Choline-Deficient Diet via Upregulation of Hepatocyte-Derived Lipocalin-2
Abstract
1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Isolation of Bone Marrow-Derived Macrophages (BMDMs)
2.3. Isolation of Liver Parenchymal and Non-Parenchymal Cells
2.4. Body Composition Analysis
2.5. Enzyme-Linked Immunosorbent Assay (ELISA)
2.6. Tissue Collection and Histological Analysis
2.7. Measurement of Liver Aspartate Alanine Aminotransferase (ALT) and Aminotransferase (AST) Concentrations
2.8. Hepatic Triglyceride (TG) Colorimetric Assay
2.9. Hepatic Hydroxyproline Assay
2.10. MASLD Activity Score Measurement
2.11. Tissue Fractionation and Western Blot Analysis
2.12. Cytokine and Chemokine Array
2.13. RNA Isolation and Quantitative Real-Time PCR (RT-PCR)
2.14. Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) Assay
2.15. Immunohistochemistry
2.16. Transmission Electron Microscopy (TEM)
2.17. Statistical Analysis
3. Results
3.1. Generation of Myeloid-Specific STAT3-Deleted Mice
3.2. Myeloid-Specific STAT3 Deletion Reduces Intrahepatic Lipid Accumulation in MCD Diet-Fed Mice
3.3. Myeloid-Specific STAT3 Deletion Promotes Hepatic Fibrosis in MCD Diet-Fed Mice
3.4. Myeloid STAT3 Deletion Increases Hepatic STAT3 and LCN2 Proteins
3.5. mSTAT3KO Mice Are More Susceptible to MCD Diet-Induced Hepatic Inflammation
3.6. mSTAT3KO Mice Are More Susceptible to MCD Diet-Induced Hepatocyte Apoptosis
3.7. Myeloid-Specific STAT3 Deletion Decreases Hepatic Peroxisome Activity in MCD Diet-Fed Mice
3.8. Myeloid-Specific STAT3 Deletion Reduces MCD Diet-Induced Mitochondrial FA Oxidation and Oxidative Stress
3.9. Myeloid-Specific STAT3 Deletion Impairs Hepatic Autophagic Flux in MCD Diet-Fed Mice
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Kim, K.E.; Shin, H.J.; An, H.S.; Jeong, E.A.; Sun, Y.; Oh, J.; Park, J.; Lee, J.; Im, S.-S.; Roh, G.S. Myeloid-Specific STAT3 Deletion Aggravates Liver Fibrosis in Mice Fed a Methionine- and Choline-Deficient Diet via Upregulation of Hepatocyte-Derived Lipocalin-2. Cells 2025, 14, 1522. https://doi.org/10.3390/cells14191522
Kim KE, Shin HJ, An HS, Jeong EA, Sun Y, Oh J, Park J, Lee J, Im S-S, Roh GS. Myeloid-Specific STAT3 Deletion Aggravates Liver Fibrosis in Mice Fed a Methionine- and Choline-Deficient Diet via Upregulation of Hepatocyte-Derived Lipocalin-2. Cells. 2025; 14(19):1522. https://doi.org/10.3390/cells14191522
Chicago/Turabian StyleKim, Kyung Eun, Hyun Joo Shin, Hyeong Seok An, Eun Ae Jeong, Yundong Sun, Jiwon Oh, Jiwoo Park, Jaewoong Lee, Seung-Soon Im, and Gu Seob Roh. 2025. "Myeloid-Specific STAT3 Deletion Aggravates Liver Fibrosis in Mice Fed a Methionine- and Choline-Deficient Diet via Upregulation of Hepatocyte-Derived Lipocalin-2" Cells 14, no. 19: 1522. https://doi.org/10.3390/cells14191522
APA StyleKim, K. E., Shin, H. J., An, H. S., Jeong, E. A., Sun, Y., Oh, J., Park, J., Lee, J., Im, S.-S., & Roh, G. S. (2025). Myeloid-Specific STAT3 Deletion Aggravates Liver Fibrosis in Mice Fed a Methionine- and Choline-Deficient Diet via Upregulation of Hepatocyte-Derived Lipocalin-2. Cells, 14(19), 1522. https://doi.org/10.3390/cells14191522