Punicalagin Ameliorates Lupus Nephritis via Inhibition of PAR2
Abstract
:1. Introduction
2. Results
2.1. Identification of a Novel PAR2 Antagonist, Punicalagin
2.2. Specific Inhibition of PAR2 by PCG in a Human Podocyte Cell Line
2.3. Inhibition of the Intracellular Signaling Pathway of PAR2 by PCG
2.4. Suppression of the PAR2-Induced Upregulation of Pro-Inflammatory Cytokines by PCG
2.5. PCG Improves Survival and Proteinuria in NZB/W F1 Mice
2.6. PCG Reduces Glomerular and Tubular Damage and Immune Deposits in Renal Glomeruli
2.7. PCG Reduces Immune Deposits in Renal Glomeruli
2.8. PCG Rebalances Serum Inflammatory Cytokines
2.9. Reduction of Spleen Size and Splenocytes by PCG
2.10. Rebalance of Splenic CD4+ T Cell Subsets by PCG
2.11. PCG Reduces Anti-Double-Stranded DNA (dsDNA) and LN-Specific IgG Subclasses
2.12. PCG Reduces VCAM-1 and ICAM-1 Expression in Kidney Tissues of Lupus-Prone Mice
2.13. Toxicity of PCG
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Cell Culture
4.3. Cell-Based Screening
4.4. Intracellular Calcium Measurement
4.5. Immunoblotting
4.6. Measurement of Cytokine Production In Vitro
4.7. Lupus-Prone Mice and Treatment Protocol
4.8. Measurement of Proteinuria
4.9. Measurement of Serum Creatinine
4.10. Renal Histopathology
4.11. Immunofluorescence
4.12. Serum Cytokine Measurement
4.13. Serum Anti-dsDNA and Immunoglobulin G (IgG) Subclass Measurement
4.14. Immunohistochemistry
4.15. Statistical Analyses
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
PCG | punicalagin |
PAR2 | protease activated receptor 2 |
LN | lupus nephritis |
SLE | systemic lupus erythematosus |
NF-κB | nuclear factor kappa B |
ERK1/2 | extracellular signal-regulated kinases 1 and 2 |
ICAM | intercellular adhesion molecule |
VCAM | vascular cell adhesion molecule |
IL | interleukin |
IFN | interferon |
TNF | tumor necrosis factor |
H&E | hematoxylin and eosin |
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Seo, Y.; Mun, C.H.; Park, S.-H.; Jeon, D.; Kim, S.J.; Yoon, T.; Ko, E.; Jo, S.; Park, Y.-B.; Namkung, W.; et al. Punicalagin Ameliorates Lupus Nephritis via Inhibition of PAR2. Int. J. Mol. Sci. 2020, 21, 4975. https://doi.org/10.3390/ijms21144975
Seo Y, Mun CH, Park S-H, Jeon D, Kim SJ, Yoon T, Ko E, Jo S, Park Y-B, Namkung W, et al. Punicalagin Ameliorates Lupus Nephritis via Inhibition of PAR2. International Journal of Molecular Sciences. 2020; 21(14):4975. https://doi.org/10.3390/ijms21144975
Chicago/Turabian StyleSeo, Yohan, Chin Hee Mun, So-Hyeon Park, Dongkyu Jeon, Su Jeong Kim, Taejun Yoon, Eunhee Ko, Sungwoo Jo, Yong-Beom Park, Wan Namkung, and et al. 2020. "Punicalagin Ameliorates Lupus Nephritis via Inhibition of PAR2" International Journal of Molecular Sciences 21, no. 14: 4975. https://doi.org/10.3390/ijms21144975