ER Stress-Perturbed Intracellular Protein O-GlcNAcylation Aggravates Podocyte Injury in Diabetes Nephropathy
Abstract
:1. Introductions
2. Results
2.1. ER Stress Is Induced in Both Type 1 and Type 2 DN
2.2. Increased Protein O-GlcNAcylation Is Identified in the Glomeruli of the DN Mice
2.3. O-GlcNAc Protein Modification Is Increased in Podocytes
2.4. An Increase in O-GlcNAc Modification Is Correlated with ER Stress
2.5. Pharmacological Mediation of Protein O-GlcNAcylation in Podocyte Injuries
2.6. ER Stress Drives O-GlcNAc Protein Modification In Vitro
3. Discussion
4. Materials and Methods
4.1. Animal Study
4.2. STZ Plus Unilateral Nephrectomy-Induced Diabetic Kidney Nephropathy Model
4.3. Unilateral Nephrectomy-Induced Diabetic Kidney Nephropathy in db/db Mice
4.4. Immunofluorescence Staining
4.5. Immunohistochemistry Staining
4.6. Immunoblotting
4.7. Cell Culture and Treatments
4.8. Flow Cytometry Analysis
4.9. Nephroseq V5 Data Acquisition
4.10. Transmission Electron Microscopy
4.11. Magnetic Microbeads Podocyte Pull-down Assay
4.12. Plasma Analysis
4.13. Statistical Analysis
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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ND | db/m | STZ plus UNx | db/db plus UNx | |
---|---|---|---|---|
Body weight, baseline (g) | 24.4 ± 2.71 | 23.67 ± 3.66 | 24.8 ± 3.21 | 29.5 ± 3.72 |
Body weight, endpoint (g) | 34.7 ± 2.44 | 36.72 ± 4.23 | 25.9 ± 2.62 * | 42.3 ± 3.87 # |
Glucose, baseline (mmol/L) | 5.3 ± 0.65 | 6.11 ± 0.35 | 4.7 ± 0.67 | 14.3 ± 3.41 |
Glucose, endpoint (mmol/L) | 4.9 ± 0.52 | 5.54 ± 0.46 | 26.7 ± 4.46 * | 28.3 ± 4.84 # |
Plasma creatinine (mg/dL) | 0.22 ± 0.07 | 0.16 ± 0.09 | 0.53 ± 0.06 * | 0.62 ± 0.10 # |
Plasma BUN (mg/dL) | 19.62 ± 4.66 | 17.34 ± 5.72 | 28.55 ± 6.86 * | 35.69 ± 5.12 # |
Urinary albumin excretion (mg/d) | 8.67 ± 2.88 | 9.32 ± 3.31 | 233.72 ± 65.43 * | 271.26 ± 73.41 # |
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Song, S.; Hu, T.; Shi, X.; Jin, Y.; Liu, S.; Li, X.; Zou, W.; Wang, C. ER Stress-Perturbed Intracellular Protein O-GlcNAcylation Aggravates Podocyte Injury in Diabetes Nephropathy. Int. J. Mol. Sci. 2023, 24, 17603. https://doi.org/10.3390/ijms242417603
Song S, Hu T, Shi X, Jin Y, Liu S, Li X, Zou W, Wang C. ER Stress-Perturbed Intracellular Protein O-GlcNAcylation Aggravates Podocyte Injury in Diabetes Nephropathy. International Journal of Molecular Sciences. 2023; 24(24):17603. https://doi.org/10.3390/ijms242417603
Chicago/Turabian StyleSong, Shicong, Tiantian Hu, Xu Shi, Yongjie Jin, Sirui Liu, Xuehong Li, Wei Zou, and Cheng Wang. 2023. "ER Stress-Perturbed Intracellular Protein O-GlcNAcylation Aggravates Podocyte Injury in Diabetes Nephropathy" International Journal of Molecular Sciences 24, no. 24: 17603. https://doi.org/10.3390/ijms242417603
APA StyleSong, S., Hu, T., Shi, X., Jin, Y., Liu, S., Li, X., Zou, W., & Wang, C. (2023). ER Stress-Perturbed Intracellular Protein O-GlcNAcylation Aggravates Podocyte Injury in Diabetes Nephropathy. International Journal of Molecular Sciences, 24(24), 17603. https://doi.org/10.3390/ijms242417603