Signal Transducer and Activator of Transcription 3 (STAT3) Suppresses STAT1/Interferon Signaling Pathway and Inflammation in Senescent Preadipocytes
Abstract
:1. Introduction
2. Materials and Methods
2.1. The 3T3-L1 Cell Culture and Senescence Induction Protocol
2.2. Mouse Experiments
2.3. Experiments on Human Adipose Tissue Samples
2.4. Senescence Associated β-Galactosidase (SA-β-Gal) Staining
2.5. Growth Curve
2.6. Western Blotting
2.7. Quantitative Polymerase Chain Reaction (qPCR)
2.8. Adipocyte Differentiation and Oil Red O Staining
2.9. Transcriptomics and Ingenuity Pathway Analysis (IPA)
2.10. Dot Blotting
2.11. Generation of Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR Associated Protein 9 (CRISPR/Cas9) Lentiviruses
2.12. Data Analysis and Statistics
3. Results
3.1. Induced Senescence in 3T3-L1 Preadipocytes with Repeated H2O2 Treatment Impairs Adipogenesis
3.2. Transcriptomics and Enriched Pathway Analysis Uncover Critical Activated Pro-Inflammatory Pathways in Senescent Preadipocytes
3.3. Oxidative Stress Promotes Senescence-Associated Secretory Phenotype (SASP) Secretion, Interferon Signaling and Signal Transducer and Activator of Transcription 1 (STAT1) Expression in Senescent 3T3-L1 Preadipocytes
3.4. Oxidative Stress Activates STAT1 and STAT3 and Promotes Induction of Their Targets
3.5. GMP-AMP Synthase-Stimulator of Interferon Genes (cGAS-STING) Pathway Regulates C-X-C Motif Chemokine Ligand 10 (CXCL10) and Type I Interferon Effector Molecules in Preadipocytes
3.6. STAT1 and STAT3 Exhibit Opposing Functions in Regulating Senescence-Associated Growth Arrest Phenotype
3.7. STAT3 Aantagonizes STAT1 Regulation of STING and Downstream Molecules
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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Madani, A.Y.; Majeed, Y.; Abdesselem, H.B.; Agha, M.V.; Vakayil, M.; Sukhun, N.K.A.; Halabi, N.M.; Kumar, P.; Hayat, S.; Elrayess, M.A.; et al. Signal Transducer and Activator of Transcription 3 (STAT3) Suppresses STAT1/Interferon Signaling Pathway and Inflammation in Senescent Preadipocytes. Antioxidants 2021, 10, 334. https://doi.org/10.3390/antiox10020334
Madani AY, Majeed Y, Abdesselem HB, Agha MV, Vakayil M, Sukhun NKA, Halabi NM, Kumar P, Hayat S, Elrayess MA, et al. Signal Transducer and Activator of Transcription 3 (STAT3) Suppresses STAT1/Interferon Signaling Pathway and Inflammation in Senescent Preadipocytes. Antioxidants. 2021; 10(2):334. https://doi.org/10.3390/antiox10020334
Chicago/Turabian StyleMadani, Aisha Y., Yasser Majeed, Houari B. Abdesselem, Maha V. Agha, Muneera Vakayil, Nour K. Al Sukhun, Najeeb M. Halabi, Pankaj Kumar, Shahina Hayat, Mohamed A. Elrayess, and et al. 2021. "Signal Transducer and Activator of Transcription 3 (STAT3) Suppresses STAT1/Interferon Signaling Pathway and Inflammation in Senescent Preadipocytes" Antioxidants 10, no. 2: 334. https://doi.org/10.3390/antiox10020334
APA StyleMadani, A. Y., Majeed, Y., Abdesselem, H. B., Agha, M. V., Vakayil, M., Sukhun, N. K. A., Halabi, N. M., Kumar, P., Hayat, S., Elrayess, M. A., Rafii, A., Suhre, K., & Mazloum, N. A. (2021). Signal Transducer and Activator of Transcription 3 (STAT3) Suppresses STAT1/Interferon Signaling Pathway and Inflammation in Senescent Preadipocytes. Antioxidants, 10(2), 334. https://doi.org/10.3390/antiox10020334