Contribution of Autophagy-Notch1-Mediated NLRP3 Inflammasome Activation to Chronic Inflammation and Fibrosis in Keloid Fibroblasts
Abstract
:1. Introduction
2. Results
2.1. Clinical Characteristics of Patients with Keloid
2.2. Notch1, α-SMA, and TGF-β3 Protein Levels are Increased in Keloid Fibroblasts
2.3. Autophagy is Disturbed in Keloid Fibroblasts
2.4. NLRP3 Inflammasome Formation is Activated in Keloid Fibroblasts
2.5. Notch Inhibition with siRNA Down-Regulates the Activation of NLRP3 Inflammasome Formation and the Differentiation into Myofibroblasts
2.6. Treatment of Keloid Fibroblasts with Rapamycin Reduces Increased Levels of Inflammasomes and TGF- β3 Proteins
3. Discussion
4. Materials and Methods
4.1. Patients and Samples
4.2. Cell Culture
4.3. Quantitative Real-Time PCR (qRT-PCR)
4.4. Western Blot Analysis
4.5. siRNA Transfection
4.6. Drug Treatment
4.7. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
ASC | Apoptosis-associated speck-like protein containing a CARD |
α-SMA | Alpha-smooth muscle actin |
DAMP | Damage-associated molecular pattern |
ECM | Extracellular matrix |
HMGB1 | High mobility group box 1 |
IL | Interleukin |
mTOR | Mammalian target of rapamycin |
NF-κB | Nuclear factor kappa B |
NICD | Notch intracellular domain |
NLRP3 | NACHT, LRR, and PYD domains-containing protein 3 |
PAMP | Pathogen-associated molecular pattern |
PCNA | Proliferating cell nuclear antigen |
qRT-PCR | Quantitative real-time polymerase chain reaction |
TGF-β | Transforming growth factor beta |
TLR | Toll-like receptor |
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Keloid1 | Keloid2 | Keloid3 | Keloid4 | Keloid5 | Keloid6 | |
---|---|---|---|---|---|---|
Gender/age | F/26 | F/25 | F/65 | F/20 | F/18 | F/23 |
Disease duration | 1 yr | 2 yrs | 3 yrs | 3 yrs | 1 yr | 2 yrs |
Symptoms | (−) | Pain, pruritus Size increasing | Pain, pruritus Size increasing | (−) | Pain, pruritus Size increasing | (−) |
Clinical findings | Not available | |||||
Previous treatment | No | ILI 1 month before excision | ILI 4 months before excision | No | No | No |
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Lee, S.; Kim, S.K.; Park, H.; Lee, Y.J.; Park, S.H.; Lee, K.J.; Lee, D.G.; Kang, H.; Kim, J.E. Contribution of Autophagy-Notch1-Mediated NLRP3 Inflammasome Activation to Chronic Inflammation and Fibrosis in Keloid Fibroblasts. Int. J. Mol. Sci. 2020, 21, 8050. https://doi.org/10.3390/ijms21218050
Lee S, Kim SK, Park H, Lee YJ, Park SH, Lee KJ, Lee DG, Kang H, Kim JE. Contribution of Autophagy-Notch1-Mediated NLRP3 Inflammasome Activation to Chronic Inflammation and Fibrosis in Keloid Fibroblasts. International Journal of Molecular Sciences. 2020; 21(21):8050. https://doi.org/10.3390/ijms21218050
Chicago/Turabian StyleLee, Seongju, Sun Kyeon Kim, Hyungsun Park, Yu Jin Lee, Song Hee Park, Kyung Jae Lee, Dong Geon Lee, Hoon Kang, and Jung Eun Kim. 2020. "Contribution of Autophagy-Notch1-Mediated NLRP3 Inflammasome Activation to Chronic Inflammation and Fibrosis in Keloid Fibroblasts" International Journal of Molecular Sciences 21, no. 21: 8050. https://doi.org/10.3390/ijms21218050