Inhibition of Xanthine Oxidase Protects against Diabetic Kidney Disease through the Amelioration of Oxidative Stress via VEGF/VEGFR Axis and NOX-FoxO3a-eNOS Signaling Pathway
Abstract
:1. Introduction
2. Results
2.1. The Effects of XO Inhibition on Physical and Biochemical Parameters in STZ-Induced DKD Mice
2.2. The Effects of XO Inhibition on Uric Acid and XOR Activities in STZ-Induced DKD Mice
Cont | Feb | STZ | STZ + Feb | |
---|---|---|---|---|
BW (g) | 29.6 ± 0.8 | 27.0 ± 2.1 | 22.2 ± 2.0 ***,†† | 22.6 ± 2.6 ***,†† |
Food intake (g/day) | 3.86 ± 0.20 | 3.20 ± 0.33 | 5.60 ± 0.13 ***,††† | 6.17 ± 0.38 ***,††† |
Water intake (mL/day) | 6.33 ± 1.04 | 4.53 ± 0.23 | 23.4 ± 0.88 ***,††† | 24.2 ± 2.46 ***,††† |
KW/BW(g/g × 100) | 0.7 ± 0.07 | 0.6 ± 0.06 | 0.9 ± 0.02 *,†† | 0.7 ± 0.1 ‡ |
FBS (mg/dL) | 180.0 ± 22.3 | 172.8 ± 25.3 | 681.0 ± 155.2 *** | 489.9 ± 39.0 ***,†† |
HbA1c (%) | 4.23 ± 0.31 | 4.16 ± 0.32 | 11.3 ± 1.32 ***,††† | 10.1 ± 1.48 ***,††† |
Serum Cr (mg/dL) | 0.08 ± 0.05 | 0.08 ± 0.04 | 0.07 ± 0.05 | 0.04 ± 0.05 |
2.3. The Effects of XO Inhibition on Renal Histological Changes, and Expression of TGF-β1 and Col IV in STZ-Induced DKD Mice
2.4. The Effects of XO Inhibition on VEGF and VEGFR Expression in STZ-Induced DKD Mice
2.5. The Effects of XO Inhibition on NOX Expressions in STZ-Induced DKD Mice
2.6. The Effects of XO Inhibition on Akt, FoxOs, and eNOS Expression in STZ-Induced DKD Mice
2.7. The Effects of XO Inhibition on Oxidative Stress in STZ-Induced DKD Mice
2.8. The Effects of XO Inhibition on Oxidative Stress in HG-Treated Human GECs via VEGFR1/3-Dependent NOX-FoxO3a-eNOS Signaling
3. Discussion
4. Materials and Methods
4.1. Animals and Experimental Design
4.2. The Assessments of Biochemical Parameters in Blood and Urine Samples
4.3. Histopathologic Analysis and Immunohistochemical Staining
4.4. In Vitro Experiments
4.5. Enzyme Immunoassay in the Kidney Tissues
4.6. Immunoblot Analysis
4.7. Real-Time Reverse Transcription Polymerase Chain Reaction (qRT-PCR)
4.8. Measurement of ROS in GECs
4.9. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Gene | Sequence (Mouse) |
---|---|
VEGF | Fwd: CAGGCTGCTGTAACGATGAA Rev: AAATGCTTTCTCCGCTCTGA |
NoxO1 | Fwd: GACATTTGCCTTCTCCGTGT Rev: CGTACCAGTCCTCGACCAGT |
p22Phox | Fwd: TGGACGTTTCACACAGTGGT Rev: ACCGACAACAGGAAGTGGAG |
p47Phox | Fwd: ACCTGAAACTGCCCACTGAC Rev: CTGTTCCCGAACTCTTCTCG |
p67Phox | Fwd: TGGCCTACTTCCAGAGAGGA Rev: CTTCATGTTGGTTGCCAATG |
mGAPDH | Fwd: TGCAGTGGCAAAGTGGAGATT Rev: CGTGAGTGGAGTCATACTGGAACA |
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Yang, K.-J.; Choi, W.J.; Chang, Y.-K.; Park, C.W.; Kim, S.Y.; Hong, Y.A. Inhibition of Xanthine Oxidase Protects against Diabetic Kidney Disease through the Amelioration of Oxidative Stress via VEGF/VEGFR Axis and NOX-FoxO3a-eNOS Signaling Pathway. Int. J. Mol. Sci. 2023, 24, 3807. https://doi.org/10.3390/ijms24043807
Yang K-J, Choi WJ, Chang Y-K, Park CW, Kim SY, Hong YA. Inhibition of Xanthine Oxidase Protects against Diabetic Kidney Disease through the Amelioration of Oxidative Stress via VEGF/VEGFR Axis and NOX-FoxO3a-eNOS Signaling Pathway. International Journal of Molecular Sciences. 2023; 24(4):3807. https://doi.org/10.3390/ijms24043807
Chicago/Turabian StyleYang, Keum-Jin, Won Jung Choi, Yoon-Kyung Chang, Cheol Whee Park, Suk Young Kim, and Yu Ah Hong. 2023. "Inhibition of Xanthine Oxidase Protects against Diabetic Kidney Disease through the Amelioration of Oxidative Stress via VEGF/VEGFR Axis and NOX-FoxO3a-eNOS Signaling Pathway" International Journal of Molecular Sciences 24, no. 4: 3807. https://doi.org/10.3390/ijms24043807