Pirfenidone Reverts Global DNA Hypomethylation, Promoting DNMT1/UHRF/PCNA Coupling Complex in Experimental Hepatocarcinoma
Abstract
:1. Introduction
2. Material and Methods
2.1. Experimental Animals
2.2. Animals and Experimental Design
2.3. Biochemical Determination of γ-GTP and ALT
2.4. Histologic Assessment of Liver Sections
2.5. Cell Culture and Treatments
2.6. Proteins Extraction and Western Blot Assay
2.7. Immunofluorescence
2.8. Global Methylation Assessment in Genomic DNA
2.9. Dot Blot of Global DNA Methylation
2.10. Protein–Protein Interaction Analysis through the STRING Platform
2.11. Molecular Docking Protein–Protein
2.12. Statistical Analysis
3. Results
3.1. Liver Damage Caused by Chemicals Is Prevented by Pirfenidone
3.2. Pirfenidone Slows down the Expression of Carcinogenic Markers, Reduces Fibrosis, and Decreases Damage in Liver Architecture
3.3. Pirfenidone Regulates Expression and Translocation of PPARγ and PPARγ2
3.4. Pirfenidone Reverses Global DNA Hypomethylation through Regulation of DNMT1
3.5. Pirfenidone Regulates DNMT1 Expression and Prevents Global DNA Hypomethylation In Vitro
3.6. In Silico Analysis Reveals That PPARγ Complexes with DNMT1
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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Groups | No of Rats with Nodules/Total Rats | Nodule Incidence (%) | Total No. of Nodules | Average No. of Nodules/Nodule Bearing Liver (Nodule Multiplicity) | Nodules Relative to Size (% of Total No.) | ||
---|---|---|---|---|---|---|---|
≥3 mm | <3 to >1 mm | ≤1 mm | |||||
NT | 0/0 | 0 | 0 | 0 | 0 | 0 | 0 |
HCC | 6/6 | 100 | 424 | 106 ± 36.36 | 12 | 30 | 58 |
HCC/PFD | 6/6 | 90 | 227 | 57 ± 12.66 | 8 | 15 | 76 |
Histological Parameter | NT | HCC | HCC/PFD |
---|---|---|---|
Hyperplasia | − | + | + |
Dysplasia | − | + | − |
Cancer cell | − | + (MD) | + (WD) |
Cellular infiltration | − | 1 | 0 |
Fibrosis | − | 3 | 2 |
Oval cells | − | 3 | 1 |
Ballooning degeneration | − | 3 | 1 |
Steatosis | − | ++ | − |
Cholestasis | − | 0 | 0 |
Mallory bodies | − | + | − |
Lobular inflammation | − | 1 | 0 |
Periportal bile ducts proliferation | − | 1 | 0 |
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Miranda-Roblero, H.O.; Saavedra-Salazar, L.F.; Galicia-Moreno, M.; Arceo-Orozco, S.; Caloca-Camarena, F.; Sandoval-Rodriguez, A.; García-Bañuelos, J.; Frias-Gonzalez, C.; Almeida-López, M.; Martínez-López, E.; et al. Pirfenidone Reverts Global DNA Hypomethylation, Promoting DNMT1/UHRF/PCNA Coupling Complex in Experimental Hepatocarcinoma. Cells 2024, 13, 1013. https://doi.org/10.3390/cells13121013
Miranda-Roblero HO, Saavedra-Salazar LF, Galicia-Moreno M, Arceo-Orozco S, Caloca-Camarena F, Sandoval-Rodriguez A, García-Bañuelos J, Frias-Gonzalez C, Almeida-López M, Martínez-López E, et al. Pirfenidone Reverts Global DNA Hypomethylation, Promoting DNMT1/UHRF/PCNA Coupling Complex in Experimental Hepatocarcinoma. Cells. 2024; 13(12):1013. https://doi.org/10.3390/cells13121013
Chicago/Turabian StyleMiranda-Roblero, Hipolito Otoniel, Liliana Faridi Saavedra-Salazar, Marina Galicia-Moreno, Scarlet Arceo-Orozco, Fernando Caloca-Camarena, Ana Sandoval-Rodriguez, Jesús García-Bañuelos, Claudia Frias-Gonzalez, Mónica Almeida-López, Erika Martínez-López, and et al. 2024. "Pirfenidone Reverts Global DNA Hypomethylation, Promoting DNMT1/UHRF/PCNA Coupling Complex in Experimental Hepatocarcinoma" Cells 13, no. 12: 1013. https://doi.org/10.3390/cells13121013
APA StyleMiranda-Roblero, H. O., Saavedra-Salazar, L. F., Galicia-Moreno, M., Arceo-Orozco, S., Caloca-Camarena, F., Sandoval-Rodriguez, A., García-Bañuelos, J., Frias-Gonzalez, C., Almeida-López, M., Martínez-López, E., Armendariz-Borunda, J., & Monroy-Ramirez, H. C. (2024). Pirfenidone Reverts Global DNA Hypomethylation, Promoting DNMT1/UHRF/PCNA Coupling Complex in Experimental Hepatocarcinoma. Cells, 13(12), 1013. https://doi.org/10.3390/cells13121013