KLF10 Inhibits TGF-β-Mediated Activation of Hepatic Stellate Cells via Suppression of ATF3 Expression
Abstract
:1. Introduction
2. Results
2.1. ATF3 Is Upregulated in Fibrotic Livers of HSD-Fed KLF10 KO Mice and in Activated HSCs
2.2. KLF10 Silencing Promotes TGF-β-Mediated Activation of HSCs via ATF3 Upregulation
2.3. KLF10 Suppresses TGF-β-Mediated Activation in HSCs
2.4. 4-PBA Treatment Suppresses siKLF10-Mediated Upregulation of ATF3 and Fibrogenic Responses in LX-2 Cells Treated with TGF-β
3. Discussion
4. Materials and Methods
4.1. RNA Sequencing and Gene Set Enrichment Analysis
4.2. Cell Culture
4.3. RNA Extraction, Reverse Transcription, and Real-Time Quantitative PCR (qPCR)
4.4. Cell Transfection
4.5. Cell Viability Analysis
4.6. Western Blot Analysis
4.7. Antibodies
4.8. Sirius Red Staining
4.9. Luciferase Reporter Assays
4.10. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
α-SMA | Alpha smooth muscle actin |
4-PBA | 4-Phenylbutyric acid |
ATF3 | Activating transcription factor 3 |
Col1α1 | Collagen type I alpha 1 |
DEG | Differentially expressed gene |
GO | Gene ontology |
HSC | Hepatic stellate cell |
HSD | High-sucrose diet |
KLF10 | Krüppel-like factor 10 |
KO | Knockout |
SMAD | Suppressor of mothers against decapentaplegic |
TGF-β1 | Transforming growth factor-beta1 |
WT | Wildtype |
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Hwang, S.; Park, S.; Yaseen, U.; Lee, H.-J.; Cha, J.-Y. KLF10 Inhibits TGF-β-Mediated Activation of Hepatic Stellate Cells via Suppression of ATF3 Expression. Int. J. Mol. Sci. 2023, 24, 12602. https://doi.org/10.3390/ijms241612602
Hwang S, Park S, Yaseen U, Lee H-J, Cha J-Y. KLF10 Inhibits TGF-β-Mediated Activation of Hepatic Stellate Cells via Suppression of ATF3 Expression. International Journal of Molecular Sciences. 2023; 24(16):12602. https://doi.org/10.3390/ijms241612602
Chicago/Turabian StyleHwang, Soonjae, Sangbin Park, Uzma Yaseen, Ho-Jae Lee, and Ji-Young Cha. 2023. "KLF10 Inhibits TGF-β-Mediated Activation of Hepatic Stellate Cells via Suppression of ATF3 Expression" International Journal of Molecular Sciences 24, no. 16: 12602. https://doi.org/10.3390/ijms241612602